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Nevertheless, its underlying pathological mechanisms remain poorly understood. Here, we showed that E3 ubiquitin ligase RING finger protein 10 (RNF10) protein levels were positively correlated with MASLD in both mice and humans. Hepatocyte-specific\n                    <jats:italic>Rnf10<\/jats:italic>\n                    deletion attenuated liver steatosis, inflammation, and fibrosis. Conversely, adeno-associated virus\u2013mediated hepatocyte-specific\n                    <jats:italic>Rnf10<\/jats:italic>\n                    overexpression exacerbated MASLD-related phenotypes. Mechanistically, RNF10 interacted with carnitine palmitoyltransferase 1A and facilitated its degradation through K48-linked ubiquitination, thereby inhibiting fatty acid oxidation, promoting hepatic lipid accumulation, and ultimately exacerbating liver inflammation and fibrosis. Moreover, we utilized triantennary\n                    <jats:italic>N<\/jats:italic>\n                    -acetylgalactosamine to deliver siRNA specifically targeting\n                    <jats:italic>Rnf10<\/jats:italic>\n                    to hepatocytes. This approach effectively ameliorated diet-induced liver steatosis, inflammation, and fibrosis in mice. Therefore, interfering with the expression or function of RNF10 may be a promising therapeutic strategy for MASLD.\n                  <\/jats:p>","DOI":"10.1172\/jci194148","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:38:41Z","timestamp":1786466321000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting the E3 ubiquitin ligase RNF10 ameliorates metabolic dysfunction\u2013associated steatohepatitis in mice"],"prefix":"10.1172","volume":"136","author":[{"given":"Chunyuan","family":"Du","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular Homeostasis and Disease, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin Medical University, Tianjin, 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