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Cancer\u2010associated missense mutations within its ubiquitin C\u2010terminal hydrolase (UCH) domain result in structural destabilization and aggregation, contributing to various malignancies such as malignant mesothelioma and uveal melanoma. In this study, we investigated the aggregation mechanisms of highly destabilized BAP1\u2010UCH variants, including N78S, C91W, F81V, and G128R, using Thioflavin T (ThT) binding assays and AmyloFit analysis. Our results reveal that all BAP1\u2010UCH variants follow a secondary nucleation\u2010dominated aggregation model, exhibiting strong concentration dependence and significantly higher aggregation rates, which may be responsible for their impaired nuclear import, leading to increased cytosolic retention. These findings provide critical insights into how specific mutations in BAP1 drive aggregation and compromise its tumor\u2010suppressing functions inside the nucleus, thereby contributing to cancer progression.<\/jats:p>","DOI":"10.1002\/cbic.202500372","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:42:11Z","timestamp":1761658931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of BRCA1\u2010Associated Protein\u20101 (BAP1) Aggregation Properties Induced by Cancer\u2010Associated Mutations"],"prefix":"10.1002","volume":"26","author":[{"given":"Li\u2010Ching","family":"Hsiao","sequence":"first","affiliation":[{"name":"Institute of Biological Chemistry Academia Sinica  Taipei 11529 Taiwan"},{"name":"Institute of Biochemical Sciences National Taiwan University  Taipei 10617 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