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ATP6V1B2, an essential subunit of the vacuolar ATPase (V-ATPase) complex, plays a pivotal role in its function and assembly. Despite its importance, the regulatory role of ATP6V1B2 and its molecular mechanism in MASLD progression remain poorly understood. In this study, we observed a significant reduction in ATP6V1B2 expression in the serum of MASLD patients. Experimental results demonstrated that inhibiting ATP6V1B2 expression in liver cells led to increased lipid accumulation, aggravated oxidative stress, upregulation of fatty acid synthase (FASN), and impaired autophagic activity. Further investigation revealed that ATP6V1B2 promotes the lysosomal degradation of FASN by maintaining the acidic environment of lysosomes, thereby playing a crucial role in lipid metabolism regulation. These findings uncover the critical mechanism by which ATP6V1B2 contributes to MASLD development and suggest that restoring its function could offer novel therapeutic strategies for treating this condition.<\/jats:p>","DOI":"10.1038\/s41420-026-03052-8","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:13:26Z","timestamp":1774325606000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ATP6V1B2 alleviates hepatic steatosis by promoting lysosomal acidification in hepatocytes"],"prefix":"10.1038","volume":"12","author":[{"given":"Ruizi","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuji","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-5813","authenticated-orcid":false,"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"3052_CR1","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/S0140-6736(24)01811-7","volume":"404","author":"M Israelsen","year":"2024","unstructured":"Israelsen M, Francque S, Tsochatzis EA, Krag A. 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