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Here, we identify a mechanism by which N6\u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) RNA modification contributes to lysosomal membrane permeabilization (LMP) in IVDD. Single\u2010cell transcriptomic analysis of human nucleus pulposus (NP) tissues shows an enrichment of lysosomal pathway genes in severely degenerated NP cells, along with LMP and disrupted mitophagy flux. We further show that interleukin\u20101\u03b2 (IL\u20101\u03b2) induces LMP, disrupts mitophagic flux, and causes mitochondrial dysfunction in NP cells. IL\u20101\u03b2 enhances WTAP, a key part of the m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase complex, essential for m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation of ACSL4 mRNA. The m\n                    <jats:sup>6<\/jats:sup>\n                    A reader IGF2BP2 then binds and stabilizes the modified transcripts, leading to increased ACSL4 expression. Consequently, lysosomal lipid peroxidation is promoted through accumulation of arachidonic acid\u2010containing phospholipids, resulting in LMP. In a rat model, intradiscal delivery of AAV9\u2010shWTAP attenuates disc degeneration, with preserved disc height, improved extracellular matrix synthesis, and restored lysosomal function and mitophagy. Our study reveals the WTAP\/ACSL4\/IGF2BP2 axis as a mediator of IL\u20101\u03b2\u2010induced LMP via m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent lipid peroxidation, highlighting a potential therapeutic target for IVDD.\n                  <\/jats:p>","DOI":"10.1002\/advs.77401","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:33:32Z","timestamp":1787988812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ACSL4\u2010Dependent Lysosomal Lipid Peroxidation Links WTAP\u2010Mediated m\n                    <sup>6<\/sup>\n                    A Modification to Intervertebral Disc Degeneration"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7699-8941","authenticated-orcid":false,"given":"Shu","family":"Jia","sequence":"first","affiliation":[{"name":"Clinical Research Team of Spine &amp; Spinal Cord Diseases Clinical Medical Research Center Affiliated Hospital of Jining Medical University Jining Medical University  Jining Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Affiliated Hospital of Jining Medical University Jining Medical University  Jining Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laimin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging Affiliated Hospital of Jining Medical University Jining Medical University  Jining Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Affiliated Hospital of Jining Medical University Jining Medical University  Jining Shandong 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