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Here, we show that renal m5C levels are markedly decreased and the m5C methyltransferase NOP2\/Sun RNA methyltransferase 5\u00a0(NSUN5) is downregulated in HN mice. Conditional knock\u2010in (cKI) mice and mouse tubular epithelial cells overexpressing NSUN5 exhibit resistance to uric acid (UA), thereby alleviating kidney injury, inflammation, and fibrosis in HN. Bisulphite sequencing coupled with RNA sequencing identifies stearoyl\u2010CoA desaturase\u20101 (SCD1) as a direct NSUN5 target and reveals the involvement of NSUN5 in ferroptosis regulation. Mechanistically, NSUN5 installs m5C on SCD1 mRNA. The m5C reader YBX2 binds to the modified transcript, prolonging the half\u2010life of SCD1 mRNA and enhancing its stability, thereby suppressing ferroptosis. Elevated SCD1 also inhibits NF\u2010\u03baB p65 phosphorylation and nuclear translocation, dampens inflammatory responses and promotes ABCG2\u2010dependent UA excretion. Recombinant NSUN5 further ameliorates renal injury in HN. Our findings revealed a novel NSUN5\u2010mediated mechanism and highlight a potential therapeutic target for HN.<\/jats:p>","DOI":"10.1002\/advs.202521459","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T10:58:50Z","timestamp":1776769130000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NSUN5 Attenuates Renal Injury and Ferroptosis in Hyperuricaemic Nephropathy Through YBX2\u2010Dependent Stabilisation of SCD1 m5C Methylation"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiu\u2010xiu","family":"Song","sequence":"first","affiliation":[{"name":"School of Pharmacy (Anhui Medical University) Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Key Laboratory of Anti\u2010Inflammatory and Immune Medicine (Anhui Medical University) Ministry of Education Anhui Institute of Innovative Drugs Anhui Medical University  Hefei 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