BAP1 (BRCA1-Associated Protein 1) was initially identified as a protein that binds to BRCA1. BAP1 is a tumor suppressor that is believed to mediate its effects through chromatin modulation, transcriptional regulation, and possibly via the ubiquitin-proteasome system and the DNA damage response pathway. Germline mutations of BAP1 confer increased susceptibility for the development of several tumors, including uveal melanoma, epithelioid atypical Spitz tumors, cutaneous melanoma, and mesothelioma. Somatic BAP1 mutations are seen in cutaneous melanocytic tumors （epithelioid atypical Spitz tumors and melanoma）, uveal melanoma, mesothelioma, clear cell renal cell carcinoma, and other tumors. BAP1 immunohistochemistry is particularly useful in differentiating malignant mesothelioma （nuclear negative） vs. reactive mesothelial proliferation （nuclear positive）.