Acute kidney injury (AKI) is a prevalent clinical syndrome with high morbidity and mortality that frequently progresses to chronic kidney disease. Its pathogenesis involves complex interactions among oxidative stress, inflammation, and programmed cell death. Tax1-binding protein 1 (TAX1BP1) has recently emerged as a key regulator connecting selective autophagy with inflammatory signaling to protect renal function. Mechanistically, TAX1BP1 confers renal protection through two complementary pathways. As a selective autophagy receptor, it protects cellular function by clearing damaged mitochondria and pro-inflammatory substrates. Additionally, it can assemble the A20 ubiquitin-editing complex to suppress NF-κB-driven inflammation and modulate cell death. Given that TAX1BP1 overexpression attenuates renal injury in animal models, targeting this molecule represents a promising therapeutic strategy for AKI.

Enxian Chen, Chunyang Li. The Role of TAX1BP1 in Acute Kidney Injury. Academic Journal of Medicine & Health Sciences (2026), Vol. 7, Issue 2: 40-55. https://doi.org/10.25236/AJMHS.2026.070207.

[1] Hu Q, Zhang Y, Xu H, et al (2021) Association between admission serum procalcitonin and the occurrence of acute kidney injury in patients with septic shock: a retrospective cohort study. Sci Prog 104:00368504211043768. https://doi.org/10.1177/00368504211043768

[2] Gansevoort RT, Wheeler DC, Debén FM, et al (2025) The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial. Nephrol Dial Transplant: Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 40:1147–1160. https://doi.org/10.1093/ndt/gfae261

[3] Pan C, Zhao H, Cai X, et al (2024) The connection between autophagy and ferroptosis in AKI: recent advances regarding selective autophagy. Ren Fail 46:2379601. https://doi.org/10.1080/0886022X.2024.2379601

[4] Zhang Q, Yu Z (2025) The clinical value of apolipoprotein C3 combined with FAR and RWT in heart failure with preserved ejection fraction. Int J Gen Med Volume 18:3823–3835. https://doi.org/10.2147/IJGM.S532542

[5] Lin S, Wang J, Cao B, et al (2023) Cofilin-1 induces acute kidney injury via the promotion of endoplasmic reticulum stress-mediated ferroptosis. Human Cell 36:1928–1937. https://doi.org/10.1007/s13577-023-00949-9

[6] Jin H, Yang Y, Zhu X, et al (2024) DDRGK1-mediated ER-phagy attenuates acute kidney injury through ER-stress and apoptosis. Cell Death Dis 15:63. https://doi.org/10.1038/s41419-024-06449-4

[7] Cai L, Fan Q, Pang R, et al (2025) Microglia programmed cell death in neurodegenerative diseases and CNS injury. Apoptosis 30:446–465. https://doi.org/10.1007/s10495-024-02041-5

[8] X T, Y O, S S, et al (2024) SIRT1-dependent neuroprotection by resveratrol in TOCP-induced spinal cord injury: modulation of ER stress and autophagic flux. Toxics 12:. https://doi.org/10.3390/toxics12110810

[9] Hu X, Ma Z, Wen L, et al (2021) Autophagy in cisplatin nephrotoxicity during cancer therapy. Cancers 13:5618. https://doi.org/10.3390/cancers13225618

[10] Liang P, Jiang B, Li Y, et al (2018) 10.Autophagy promotes angiogenesis via AMPK/akt/mTOR signaling during the recovery of heat-denatured endothelial cells. Cell Death Dis 9:1152. https://doi.org/10.1038/s41419-018-1194-5

[11] Cao Y, Chen Z, Yin Y, et al (2025) Autophagy-dependent hepatocyte apoptosis mediates gilteritinib-induced hepatotoxicity. Toxicol Lett 410:189–196. https://doi.org/10.1016/j.toxlet.2025.06.018

[12] Shembade N, Harhaj EW (2012) Regulation of NF-κB signaling by the A20 deubiquitinase. Cell Mol Immunol 9:123–130. https://doi.org/10.1038/cmi.2011.59

[13] Su R, Kang X, Niu Y, et al (2024) PCBP1 interacts with the HTLV-1 tax oncoprotein to potentiate NF-κB activation. Front Immunol 15:. https://doi.org/10.3389/fimmu.2024.1375168

[14] Goodwin JM, Dowdle WE, DeJesus R, et al (2017) Autophagy-independent lysosomal targeting regulated by ULK1/2-FIP200 and ATG9. Cell Reports 20:2341–2356. https://doi.org/10.1016/j.celrep.2017.08.034

[15] Rogov VV, Stolz A, Ravichandran AC, et al (2017) Structural and functional analysis of the GABARAP interaction motif (GIM). EMBO Rep 18:1382–1396. https://doi.org/10.15252/embr.201643587

[16] Towards a better understanding of the neuro-developmental role of autophagy in sickness and in health. http://www.cell-stress.com/researcharticles/2021a-zapata-munoz-cell-stress/. Accessed 17 Jan 2026

[17] Dai X-G, Xu W, Li T, et al (2019) Involvement of phosphatase and tensin homolog-induced putative kinase 1–parkin-mediated mitophagy in septic acute kidney injury. Chin Med J (Engl) 132:2340. https://doi.org/10.1097/CM9.0000000000000448

[18] Chen J, Chen C, Lv C, et al (2025) Vitexin enhances mitophagy and improves renal ischemia-reperfusion injury by regulating the p38/MAPK pathway. Ren Fail 47:2463572. https://doi.org/10.1080/0886022X.2025.2463572

[19] Huang X-R, Ye L, An N, et al (2025) Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1. Autophagy 21:120–140. https://doi.org/10.1080/15548627.2024.2393926

[20] Morriswood B, Ryzhakov G, Puri C, et al (2007) T6BP and NDP52 are myosin VI binding partners with potential roles in cytokine signalling and cell adhesion. J Cell Sci 120:2574–2585. https://doi.org/10.1242/jcs.007005

[21] Fu T, Zhang M, Zhou Z, et al (2021) Structural and biochemical advances on the recruitment of the autophagy-initiating ULK and TBK1 complexes by autophagy receptor NDP52. Sci Adv. https://doi.org/10.1126/sciadv.abi6582

[22] Zhou Z, Liu J, Fu T, et al (2021) Phosphorylation regulates the binding of autophagy receptors to FIP200 claw domain for selective autophagy initiation. Nat Commun 12:1570. https://doi.org/10.1038/s41467-021-21874-1

[23] Sarraf SA, Shah HV, Kanfer G, et al (2020) Loss of TAX1BP1-directed autophagy results in protein aggregate accumulation in the brain. Mol Cell 80:779-795.e10. https://doi.org/10.1016/j.molcel.2020.10.041

[24] Zhang M, Wang Y, Gong X, et al (2024) Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins. Proc Natl Acad Sci U S A 121:e2315550121. https://doi.org/10.1073/pnas.2315550121

[25] Gibertini S, Ruggieri A, Cheli M, Maggi L (2023) Protein aggregates and aggrephagy in myopathies. Int J Mol Sci 24:8456. https://doi.org/10.3390/ijms24098456

[26] Ren H, Wang Y, Li L-F, et al (2025) The african swine fever virus p22 inhibits the JAK-STAT signaling pathway by promoting the TAX1BP1-mediated degradation of the type I interferon receptor. PLOS Pathog 21:e1013319. https://doi.org/10.1371/journal.ppat.1013319

[27] White J, Choi YB, Zhang J, et al (2025) Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes ATG8-family protein-dependent clearance of MAVS aggregates. Autophagy 21:160–177. https://doi.org/10.1080/15548627.2024.2394306

[28] White J, Suklabaidya S, Vo MT, et al (2023) Multifaceted roles of TAX1BP1 in autophagy. Autophagy 19:44–53. https://doi.org/10.1080/15548627.2022.2070331

[29] Liu Y, Wang M, Hou X-O, Hu L-F (2022) Roles of microglial mitophagy in neurological disorders. Front Aging Neurosci 14. https://doi.org/10.3389/fnagi.2022.979869

[30] Kruppa AJ, Buss F (2021) Motor proteins at the mitochondria–cytoskeleton interface. J Cell Sci 134:jcs226084. https://doi.org/10.1242/jcs.226084

[31] Lu Z, Luo R, Lan J, et al (2024) The MGF300-2R protein of african swine fever virus promotes IKKβ ubiquitination by recruiting the E3 ubiquitin ligase TRIM21. Viruses 16:949. https://doi.org/10.3390/v16060949

[32] Bullones-Bolaños A, Bernal-Bayard J, Ramos-Morales F (2022) The NEL family of bacterial E3 ubiquitin ligases. Int J Mol Sci 23:7725. https://doi.org/10.3390/ijms23147725

[33] Le Guerroué F, Bunker EN, Rosencrans WM, et al (2023) TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1. Mol Cell 83:927-941.e8. https://doi.org/10.1016/j.molcel.2023.02.023

[34] Turco E, Savova A, Gere F, et al (2021) Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Nat Commun 12:5212. https://doi.org/10.1038/s41467-021-25572-w

[35] Zhang M, Wang Y, Gong X, et al (2024) Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins. Proc Natl Acad Sci U S A 121:e2315550121. https://doi.org/10.1073/pnas.2315550121

[36] Mechanistic insights into the interactions of TAX1BP1 with RB1CC1 and mammalian ATG8 family proteins | PNAS. https://www.pnas.org/doi/10.1073/pnas.2315550121. Accessed 17 Jan 2026

[37] Yeo SK, Haas M, Manupati K, et al (2024) AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer. Autophagy 20:525–540. https://doi.org/10.1080/15548627.2023.2259775

[38] Chen, W., Shen, T., Wang, L., & Lu, K. (2021). Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates. Cells, 10(8), 1989. https://doi.org/10.3390/cells10081989

[39] Tumbarello DA, Manna PT, Allen M, et al (2015) The autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of salmonella typhimurium by autophagy. PLOS Pathogens 11:e1005174. https://doi.org/10.1371/journal.ppat.1005174

[40] Tumbarello DA, Manna PT, Allen M, et al (2016) Correction: the autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of salmonella typhimurium by autophagy. PLOS Pathog 12:e1005433. https://doi.org/10.1371/journal.ppat.1005433

[41] Huang L, Yu L-J, Zhang X, et al (2019) Autophagy regulates glucose-mediated root meristem activity by modulating ROS production in arabidopsis. Autophagy 15:407–422. https://doi.org/10.1080/15548627.2018.1520547

[42] Wu S, Shen Y, Zhang S, et al (2020) Salmonella interacts with autophagy to offense or defense. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.00721

[43] Lindsey ARI, Bhattacharya T, Hardy RW, Newton ILG (2021) Wolbachia and virus alter the host transcriptome at the interface of nucleotide metabolism pathways. mBio 12:10.1128/mbio.03472-20. https://doi.org/10.1128/mbio.03472-20

[44] Cadwell K, Abraham C, Bel S, et al (2025) Autophagy and bacterial infections. Autophagy Rep 4:2542904. https://doi.org/10.1080/27694127.2025.2542904

[45] Wilfling F, Lee C-W, Erdmann PS, et al (2020) A selective autophagy pathway for phase-separated endocytic protein deposits. Mol Cell 80:764-778.e7. https://doi.org/10.1016/j.molcel.2020.10.030

[46] Sarraf SA, Shah HV, Kanfer G, et al (2022) Loss of TAX1BP1-directed autophagy results in protein aggregate accumulation in the brain. Mol Cell 82:1383–1385. https://doi.org/10.1016/j.molcel.2022.03.020

[47] Yang Q, Liu T-T, Lin H, et al (2017) TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. PLOS Pathogens 13:e1006600. https://doi.org/10.1371/journal.ppat.1006600

[48] Samie M, Lim J, Verschueren E, et al (2018) Selective autophagy of the adaptor TRIF regulates innate inflammatory signaling. Nat Immunol 19:246–254. https://doi.org/10.1038/s41590-017-0042-6

[49] Lorentzen KC, Prescott AR, Ganley IG (2025) Artificial targeting of autophagy components to mitochondria reveals both conventional and unconventional mitophagy pathways. Autophagy 21:315–337. https://doi.org/10.1080/15548627.2024.2395149

[50] Lazarou M, Sliter DA, Kane LA, et al (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314. https://doi.org/10.1038/nature14893

[51] Park NY, Jo DS, Yang J-Y, et al (2025) Activation of lysophagy by a TBK1-SCFFBXO3-TMEM192-TAX1BP1 axis in response to lysosomal damage. Nat Commun 16:1109. https://doi.org/10.1038/s41467-025-56294-y

[52] Shembade N, Harhaj NS, Liebl DJ, Harhaj EW (2007) Essential role for TAX1BP1 in the termination of TNF‐α‐, IL‐1‐ and LPS‐mediated NF‐κB and JNK signaling. EMBO J 26:3910–3922. https://doi.org/10.1038/sj.emboj.7601823

[53] Verstrepen L, Verhelst K, Carpentier I, Beyaert R (2011) TAX1BP1, a ubiquitin-binding adaptor protein in innate immunity and beyond. Trends in Biochemical Sciences 36:347–354. https://doi.org/10.1016/j.tibs.2011.03.004

[54] Sen R, Baltimore D (1986) Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47:921–928. https://doi.org/10.1016/0092-8674(86)90807-X

[55] Oeckinghaus A, Ghosh S (2009) The NF-κB family of transcription factors and its regulation. Cold Spring Harbor Perspect Biol 1:a000034. https://doi.org/10.1101/cshperspect.a000034

[56] Liu T, Zhang L, Joo D, Sun S-C (2017) NF-κB signaling in inflammation. Signal Transduction Targeted Ther 2:17023. https://doi.org/10.1038/sigtrans.2017.23

[57] Shembade N, Pujari R, Harhaj NS, et al (2011) The kinase IKKα inhibits activation of the transcription factor NF-κB by phosphorylating the regulatory molecule TAX1BP1. Nat Immunol 12:834–843. https://doi.org/10.1038/ni.2066

[58] Shembade N, Harhaj NS, Parvatiyar K, et al (2008) The E3 ligase itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol 9:254–262. https://doi.org/10.1038/ni1563

[59] Gao L, Coope H, Grant S, et al (2011) ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral signaling *. J Biol Chem 286:36592–36602. https://doi.org/10.1074/jbc.M111.283762

[60] Yang M, Liu X, Jiang M, et al (2024) TAX1BP1/A20 inhibited TLR2-NF-κB activation to induce tolerant expression of IL-6 in endothelial cells. International Immunopharmacology 139:112789. https://doi.org/10.1016/j.intimp.2024.112789

[61] Seth RB, Sun L, Ea C-K, Chen ZJ (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3. Cell 122:669–682. https://doi.org/10.1016/j.cell.2005.08.012

[62] Meylan E, Curran J, Hofmann K, et al (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–1172. https://doi.org/10.1038/nature04193

[63] Choi YB, Shembade N, Parvatiyar K, et al (2016) TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS. Mol Cell Biol 37:e00422. https://doi.org/10.1128/MCB.00422-16

[64] Z J, Tw M, G S, X L (2004) Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc Natl Acad Sci U S A 101:3533–3538. https://doi.org/10.1073/pnas.0308496101

[65] Reggiori F, Monastyrska I, Verheije MH, et al (2010) Coronaviruses hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication. Cell Host Microbe 7:500–508. https://doi.org/10.1016/j.chom.2010.05.013

[66] Wu Z, Tan W, Wang C, et al (2025) TAX1BP1 regulates the apoptosis of renal tubular epithelial cells in ischemia/reperfusion injury via the NF-kB/PMAIP1 signaling pathway. Inflamm Res: Off J Eur Histamine Res Soc [et Al,] 74:9. https://doi.org/10.1007/s00011-024-01976-4

[67] Liu K, Czaja MJ (2013) Regulation of lipid stores and metabolism by lipophagy. Cell Death Differ 20:3–11. https://doi.org/10.1038/cdd.2012.63

[68] Zhang S, Peng X, Yang S, et al (2022) The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders. Cell Death Dis 13:132. https://doi.org/10.1038/s41419-022-04593-3

[69] Hm K, Sh A, P C, et al (2015) Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nature medicine 21. https://doi.org/10.1038/nm.3762

[70] Jang H-S, Noh MR, Kim J, Padanilam BJ (2020) Defective mitochondrial fatty acid oxidation and lipotoxicity in kidney diseases. Front Med 7:65. https://doi.org/10.3389/fmed.2020.00065

[71] Mallia A, Papaianni GG, Brocca L, et al (2025) Decoding the lipid droplet proteome: new frontiers in cardiovascular disease research. Int J Mol Sci 26:10280. https://doi.org/10.3390/ijms262110280

[72] Chung J, Park J, Lai ZW, et al (2023) The troyer syndrome protein spartin mediates selective autophagy of lipid droplets. Nat Cell Biol 25:1101–1110. https://doi.org/10.1038/s41556-023-01178-w

[73] Hu S, Guo Y, Wang Y, et al (2019) Structure of myosin VI/Tom1 complex reveals a cargo recognition mode of myosin VI for tethering. Nat Commun 10:3459. https://doi.org/10.1038/s41467-019-11481-6

[74] L W, J Z, S Y, et al (2017) Ethanol-triggered lipophagy requires SQSTM1 in AML12 hepatic cells. Sci Rep 7. https://doi.org/10.1038/s41598-017-12485-2

[75] Yan Q, Song Y, Zhang L, et al (2018) Autophagy activation contributes to lipid accumulation in tubular epithelial cells during kidney fibrosis. Cell Death Discovery 4:2. https://doi.org/10.1038/s41420-018-0065-2

[76] X M, J J, Hy L (2022) Driving role of macrophages in transition from acute kidney injury to chronic kidney disease. Chin Med J (Engl) 135. https://doi.org/10.1097/CM9.0000000000002100

[77] Radjabova V, Mastroeni P, Skjødt K, et al (2015) TARM1 is a novel leukocyte receptor complex-encoded ITAM receptor that costimulates proinflammatory cytokine secretion by macrophages and neutrophils. J Immunol 195:3149–3159. https://doi.org/10.4049/jimmunol.1401847

[78] Gottlieb RA, Andres AM, Sin J, Taylor DPJ (2015) Untangling autophagy measurements: all fluxed up. Circ Res 116:504–514. https://doi.org/10.1161/CIRCRESAHA.116.303787

[79] Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, et al (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy 17:1–382. https://doi.org/10.1080/15548627.2020.1797280

[80] Tang C, Livingston MJ, Liu Z, Dong Z (2020) Autophagy in kidney homeostasis and disease. Nat Rev Nephrol 16:489–508. https://doi.org/10.1038/s41581-020-0309-2

[81] Bauer B, Idinger J, Schuschnig M, et al (2024) Recruitment of autophagy initiator TAX1BP1 advances aggrephagy from cargo collection to sequestration. EMBO J 43:5910–5940. https://doi.org/10.1038/s44318-024-00280-5

[82] Tumbarello DA, Waxse BJ, Arden SD, et al (2012) Autophagy receptors link myosin VI to autophagosomes to mediate Tom1-dependent autophagosome maturation and fusion with the lysosome. Nat Cell Biol 14:1024–1035. https://doi.org/10.1038/ncb2589

[83] Lv L-L, Wang C, Li Z-L, et al (2021) SAP130 released by damaged tubule drives necroinflammation via miRNA-219c/mincle signaling in acute kidney injury. Cell Death Dis 12:866. https://doi.org/10.1038/s41419-021-04131-7

[84] DeWolf SE, Kasimsetty SG, Hawkes AA, et al (2022) DAMPs released from injured renal tubular epithelial cells activate innate immune signals in healthy renal tubular epithelial cells. Transplantation 106:1589–1599. https://doi.org/10.1097/TP.0000000000004038

[85] Fujiki K, Inamura H, Sugaya T, Matsuoka M (2019) Blockade of ALK4/5 signaling suppresses cadmium- and erastin-induced cell death in renal proximal tubular epithelial cells via distinct signaling mechanisms. Cell Death Differ 26:2371–2385. https://doi.org/10.1038/s41418-019-0307-8

[86] Murao A, Aziz M, Wang H, et al (2021) Release mechanisms of major DAMPs. Apoptosis: Int J Program Cell Death 26:152–162. https://doi.org/10.1007/s10495-021-01663-3

[87] Riegler AN, Benson P, Long K, Leal SM (2023) Differential activation of programmed cell death in patients with severe SARS-CoV-2 infection. Cell Death Discov 9:420. https://doi.org/10.1038/s41420-023-01715-4

[88] Zhang Y, Hu J, Zhang Y, Ci X (2025) Amentoflavone protects against cisplatin-induced acute kidney injury by modulating Nrf2-mediated oxidative stress and ferroptosis and partially by activating Nrf2-dependent PANoptosis. Front Pharmacol 16:1508047. https://doi.org/10.3389/fphar.2025.1508047

[89] Song HY, Régnier CH, Kirschning CJ, et al (1997) Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2. Proc Natl Acad Sci U S A 94:9792–9796. https://doi.org/10.1073/pnas.94.18.9792

[90] Wertz IE, O’Rourke KM, Zhou H, et al (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699. https://doi.org/10.1038/nature02794

[91] Li J, McQuade T, Siemer AB, et al (2012) The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150:339–350. https://doi.org/10.1016/j.cell.2012.06.019

[92] Duprez L, Takahashi N, Van Hauwermeiren F, et al (2011) RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity 35:908–918. https://doi.org/10.1016/j.immuni.2011.09.020

[93] Seo Y-W, Shin JN, Ko KH, et al (2003) The molecular mechanism of noxa-induced mitochondrial dysfunction in p53-mediated cell death. J Biol Chem 278:48292–48299. https://doi.org/10.1074/jbc.M308785200

[94] Martin AG, Trama J, Crighton D, et al (2009) Activation of p73 and induction of noxa by DNA damage requires NF-kappa B. Aging (Milano) 1:335–349. https://doi.org/10.18632/aging.100026

[95] Msaki A, Sánchez AM, Koh LF, et al (2011) The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration. Mol Biol Cell 22:3032–3040. https://doi.org/10.1091/mbc.E11-04-0280

[96] Oda E, Ohki R, Murasawa H, et al (2000) Noxa, a BH3-only member of the bcl-2 family and candidate mediator of p53-induced apoptosis. Sci (N Y NY) 288:1053–1058. https://doi.org/10.1126/science.288.5468.1053

[97] Huang DC, Strasser A (2000) BH3-only proteins-essential initiators of apoptotic cell death. Cell 103:839–842. https://doi.org/10.1016/s0092-8674(00)00187-2

[98] Cho YS, Challa S, Moquin D, et al (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123. https://doi.org/10.1016/j.cell.2009.05.037

[99] Wang H, Sun L, Su L, et al (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54:133–146. https://doi.org/10.1016/j.molcel.2014.03.003

[100] J L, H P, J H, et al (2019) Autophagy regulates inflammatory programmed cell death via turnover of RHIM-domain proteins. eLife 8:. https://doi.org/10.7554/eLife.44452

[101] Hou S, Zhang J, Jiang X, et al (2024) PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis. Mol Cell 84:938-954. https://doi.org/10.1016/j.molcel.2023.12.041

[102] Shembade N, Parvatiyar K, Harhaj NS, Harhaj EW (2009) The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling. EMBO J 28:513–522. https://doi.org/10.1038/emboj.2008.285

[103] Tang Y, Tu H, Zhang J, et al (2019) K63-linked ubiquitination regulates RIPK1 kinase activity to prevent cell death during embryogenesis and inflammation. Nat Commun 10:4157. https://doi.org/10.1038/s41467-019-12033-8

[104] Witt A, Vucic D (2017) Diverse ubiquitin linkages regulate RIP kinases-mediated inflammatory and cell death signaling. Cell Death Differ 24:1160–1171. https://doi.org/10.1038/cdd.2017.33

[105] H I, Jm P, L V, et al (2008) Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation. EMBO J 27. https://doi.org/10.1038/emboj.2008.5

[106] Kaiser WJ, Sridharan H, Huang C, et al (2013) Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem 288:31268–31279. https://doi.org/10.1074/jbc.M113.462341

[107] Jacque E, Ley SC (2009) RNF11, a new piece in the A20 puzzle. EMBO J 28:455–456. https://doi.org/10.1038/emboj.2009.18

[108] Shembade N, Ma A, Harhaj EW (2010) Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Sci (N Y NY) 327:1135–1139. https://doi.org/10.1126/science.1182364

[109] H X, Z H, M X, et al (2025) The role of post-translational modifications in necroptosis. Biomolecules 15. https://doi.org/10.3390/biom15040549

[110] Y F, Z C, L M, et al (2022) PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles. Journal of nanobiotechnology 20. https://doi.org/10.1186/s12951-022-01338-4

[111] Wang S, Long H, Hou L, et al (2023) The mitophagy pathway and its implications in human diseases. Signal Transduct Target Ther 8:304. https://doi.org/10.1038/s41392-023-01503-7

[112] Li Z-L, Li X-Y, Zhou Y, et al (2024) Renal tubular epithelial cells response to injury in acute kidney injury. EBioMedicine 107:105294. https://doi.org/10.1016/j.ebiom.2024.105294

[113] Verma SK, Molitoris BA (2015) Renal endothelial injury and microvascular dysfunction in acute kidney injury. Semin Nephrol 35:96–107. https://doi.org/10.1016/j.semnephrol.2015.01.010

[114] Xu C, Hong Q, Zhuang K, et al (2023) Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition. Metab, Clin Exp 145:155592. https://doi.org/10.1016/j.metabol.2023.155592

[115] Kim KP, Williams CE, Lemmon CA (2022) Cell-matrix interactions in renal fibrosis. Kidney Dial 2:607–624. https://doi.org/10.3390/kidneydial2040055

[116] Liang S, Wu Y-S, Li D-Y, et al (2022) Autophagy and renal fibrosis. Aging dis 13:712–731. https://doi.org/10.14336/AD.2021.1027

[117] Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2:1303–1353. https://doi.org/10.1002/cphy.c110041

[118] Fu Y, Xiang Y, Wei Q, et al (2024) Rodent models of AKI and AKI-CKD transition: an update in 2024. Am J Physiol Renal Physiol 326:F563–F583. https://doi.org/10.1152/ajprenal.00402.2023

[119] Gong L, Pan Q, Yang N (2020) Autophagy and inflammation regulation in acute kidney injury. Front Physiol 11:576463. https://doi.org/10.3389/fphys.2020.576463

[120] Leventhal JS, Ni J, Osmond M, et al (2016) Autophagy limits endotoxemic acute kidney injury and alters renal tubular epithelial cell cytokine expression. PLOS One 11:e0150001. https://doi.org/10.1371/journal.pone.0150001

[121] Dai R, Zhang L, Jin H, et al (2022) Autophagy in renal fibrosis: Protection or promotion? Front Pharmacol 13:963920. https://doi.org/10.3389/fphar.2022.963920

[122] Lin F (2017) Autophagy in renal tubular injury and repair. Acta Physiol (Oxf Engl) 220:229–237. https://doi.org/10.1111/apha.12852

[123] Livingston MJ, Ding H-F, Huang S, et al (2016) Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy 12:976–998. https://doi.org/10.1080/15548627.2016.1166317

[124] T Y (2025) Autophagic stagnation: a key mechanism in kidney disease progression linked to aging and obesity. Clin exp nephrol 29. https://doi.org/10.1007/s10157-025-02653-4

[125] Wu G, Liu S, Hagenstein J, et al Adeno-associated virus–based gene therapy treats inflammatory kidney disease in mice. J Clin Invest 134:e174722. https://doi.org/10.1172/JCI174722

[126] Tavakolidakhrabadi N, Ding WY, Saleem MA, et al (2024) Gene therapy and kidney diseases. Mol Ther--Methods Clin Dev 32. https://doi.org/10.1016/j.omtm.2024.101333

[127] Furusho T, Das R, Hakui H, et al (2024) Enhancing gene transfer to renal tubules and podocytes by context-dependent selection of AAV capsids. Nat Commun 15:10728. https://doi.org/10.1038/s41467-024-54475-9

[128] Peek JL, Rosales A, Qi J, et al (2025) Efficient kidney gene transfer and proximal tubule transduction using self-complementary AAV.cc47 vectors. Mol Ther, Methods Clin Dev 33:101606. https://doi.org/10.1016/j.omtm.2025.101606

[129] Ding WY, Kuzmuk V, Hunter S, et al (2023) Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome. Sci Transl Med 15:eabc8226. https://doi.org/10.1126/scitranslmed.abc8226

[130] Xu Q, Li Z-L, Zhang Y-L, et al (2025) Kidney hepcidin protects the collecting duct against ferroptosis in ischemia/reperfusion-induced acute kidney injury. Kidney Int 108:394–410. https://doi.org/10.1016/j.kint.2025.05.030

[131] Ortega-Loubon C, Fernández-Molina M, Carrascal-Hinojal Y, Fulquet-Carreras E (2016) Cardiac surgery-associated acute kidney injury. Ann Card Anaesth 19:687–698. https://doi.org/10.4103/0971-9784.191578

[132] Hong SH, Nguyen T, Ongkingco JF, et al (2025) From concepts to inhibitors: a blueprint for targeting protein-protein interactions. Chem Rev 125:6819–6869. https://doi.org/10.1021/acs.chemrev.5c00046

[133] Xie X, Yu T, Li X, et al (2023) Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials. Signal Transduction Targeted Ther 8:335. https://doi.org/10.1038/s41392-023-01589-z

[134] Soini L, Leysen S, Davis J, Ottmann C (2022) Molecular glues to stabilise protein-protein interactions. Curr Opin Chem Biol 69:102169. https://doi.org/10.1016/j.cbpa.2022.102169

[135] Békés M, Langley DR, Crews CM (2022) PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov 21:181–200. https://doi.org/10.1038/s41573-021-00371-6

[136] Murgai A, Sosič I, Gobec M, et al (2022) Targeting the deubiquitinase USP7 for degradation with PROTACs. Chem Commun Camb Engl 58:8858–8861. https://doi.org/10.1039/d2cc02094g

[137] Miao J, Zhang Z-Y (2024) Drugging protein tyrosine phosphatases through targeted protein degradation. ChemMedChem 19:e202300669. https://doi.org/10.1002/cmdc.202300669

[138] Waldner M, Fantus D, Solari M, Thomson AW (2016) New perspectives on mTOR inhibitors (rapamycin, rapalogs and TORKinibs) in transplantation. British Journal of Clinical Pharmacology 82:1158–1170. https://doi.org/10.1111/bcp.12893

[139] Su Y, Lu J, Gong P, et al (2018) Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway. Mol Med Rep 18:5445–5454. https://doi.org/10.3892/mmr.2018.9586

[140] Panwar V, Singh A, Bhatt M, et al (2023) Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduction Targeted Ther 8:375. https://doi.org/10.1038/s41392-023-01608-z

[141] B P, Ij S, Dm B, et al (2020) Large animal models for translational research in acute kidney injury. Renal failure 42. https://doi.org/10.1080/0886022X.2020.1830108

[142] Noel S, Kurzhagen JT, Lee SA, et al (2023) Kidney immune cell characterization of humanized mouse models. Kidney360 5:96. https://doi.org/10.34067/KID.0000000000000300

[143] Pode-Shakked N, Devarajan P (2022) Human stem cell and organoid models to advance acute kidney injury diagnostics and therapeutics. Int J Mol Sci 23:7211. https://doi.org/10.3390/ijms23137211

[144] Bellomo R, Kellum JA, Ronco C (2012) Acute kidney injury. Lancet (Lond Engl) 380:756–766. https://doi.org/10.1016/S0140-6736(11)61454-2

[145] Zarbock A, Nadim MK, Pickkers P, et al (2023) Sepsis-associated acute kidney injury: consensus report of the 28th acute disease quality initiative workgroup. Nat Rev, Nephrol 19:401–417. https://doi.org/10.1038/s41581-023-00683-3

[146] Chen Z, Li Y, Yuan Y, et al (2023) Single-cell sequencing reveals homogeneity and heterogeneity of the cytopathological mechanisms in different etiology-induced AKI. Cell Death Dis 14:318. https://doi.org/10.1038/s41419-023-05830-z