BAP1 (BRCA1 Associated Protein 1) is a deubiquitinating enzyme that functions as a tumor suppressor through multiple nuclear and cytoplasmic mechanisms. In the nucleus, BAP1 serves as the catalytic component of the polycomb repressive deubiquitinase (PR-DUB) complex, specifically mediating deubiquitination of histone H2A monoubiquitinated at lysine 120 (H2AK119ub1) 1. This epigenetic activity regulates gene expression by antagonizing PRC1-mediated chr3 modifications. BAP1 also deubiquitinates HCFC1, contributing to cell growth regulation 2. In the cytoplasm, BAP1 suppresses ferroptosis by repressing SLC7A11 expression, which controls cystine uptake and lipid peroxidation, thereby linking metabolic regulation to tumor suppression 1. Additionally, BAP1 can be modified by UFMylation, enhancing its interaction with and stabilization of the von Hippel-Lindau tumor suppressor protein (pVHL) 3. Germline BAP1 mutations cause a hereditary tumor predisposition syndrome associated with uveal melanoma, malignant mesothelioma, renal cell carcinoma, and cutaneous melanoma 4. Loss of BAP1 expression serves as a diagnostic biomarker for mesothelioma in situ and malignant mesothelioma 5. BAP1's context-dependent functions make it critical for tumor suppression across multiple cancer types.