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Nuclear pore protein 85 (NUP85) has been implicated in the development of various liver diseases. However, its involvement in liver fibrosis remains unclear. The present study aimed to explore the role of NUP85 in liver fibrosis. The expression level of NUP85 was found to be elevated in the liver tissues of liver fibrosis patients and mice. Knockdown of NUP85 not only ameliorated liver injury and collagen deposition, but also suppressed endoplasmic reticulum stress (ERS). Conversely, the opposite pathological and biochemical changes are observed with NUP85 overexpression. Mechanistically, NUP85 competitively binds ubiquitin\u2010specific peptidase 47 (USP47) to apoptosis signal\u2010regulating kinase 1 (ASK1), deubiquitinates lysine residue 805 of ASK1, and regulates the activation of ASK1, thereby exacerbating collagen deposition and ERS. Furthermore, we developed a CREKA\u2010coupled liposome as a targeted delivery system to deliver Mogroside V (MV), a pharmacological inhibitor of NUP85, to activated HSCs and attenuate liver fibrosis. Taken together, the present study demonstrated that NUP85 is a novel regulator of liver fibrosis and that the NUP85\u2010USP47\u2010ASK1 signaling pathway might be a strategy for therapeutic intervention.<\/jats:p>","DOI":"10.1002\/advs.202519972","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T16:46:32Z","timestamp":1774716392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NUP85 Mediates Endoplasmic Reticulum Stress through the USP47\/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis"],"prefix":"10.1002","volume":"13","author":[{"given":"Dashuai","family":"Yang","sequence":"first","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province School of Pharmacy Anhui Medical University  Hefei 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