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Disease-associated accumulation of ITCH promotes fragmentation of both the cis- and trans-Golgi networks, disrupting protein sorting and impairing lysosomal functions. The ITCH-dependent lysosomal dysfunction compromises the clearance of misfolded proteins associated with several neurodegenerative diseases. Inhibition of ITCH protects against proteotoxicity in both mammalian neurons and\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    models of neurodegeneration. The accumulation of ITCH in patients with ALS and AD is attributed to up-regulation of the ubiquitin-specific protease USP11, which deubiquitinates and stabilizes ITCH. These results uncover a pathogenic pathway regulating Golgi integrity and contributing to the development of neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ado4330","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:58:36Z","timestamp":1761328716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["ITCH regulates Golgi integrity and proteotoxicity in neurodegeneration"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4710-7572","authenticated-orcid":true,"given":"Qiwang","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, 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