BAP1, short for BRCA1-Associated Protein 1, is a ubiquitin carboxy-terminal hydrolase functioning as a tumor suppressor [1,3,4,6]. It regulates multiple crucial processes via its deubiquitinating activity, such as DNA damage repair, cell cycle control, chromatin modification, programmed cell death, and the immune response [1]. BAP1-related pathways are involved in various biological processes and are of great significance in maintaining normal cellular functions.

In functional studies, BAP1 has been shown to decrease histone 2A ubiquitination (H2Aub) on chromatin [2]. It links metabolic regulation of ferroptosis to tumour suppression by repressing the expression of cystine transporter SLC7A11, leading to elevated lipid peroxidation and ferroptosis [2]. Loss-of-function of BAP1 in normal human cholangiocyte organoids engineered by CRISPR/Cas9 results in loss of epithelial characteristics and increased motility, indicating its role in controlling epithelial identity through chromatin accessibility regulation [5].

In conclusion, BAP1 is a key tumor suppressor with diverse functions in regulating chromatin-associated processes, cell metabolism, and cell death. Its loss-of-function models, such as those in human organoids, have revealed its importance in tumor-related biological processes, especially in cancers like uveal melanoma, malignant mesothelioma, and renal cell carcinoma, which are often associated with BAP1 mutations [1,2,3,4,6,7].