BUB3 is a mitotic checkpoint protein essential for maintaining chr10 stability through dual roles in spindle assembly checkpoint (SAC) signaling and kinetochore-microtubule attachment regulation 1. As a component of the BUB1/BUB3 complex, BUB3 inhibits the anaphase-promoting complex (APC/C) by phosphorylating CDC20 when the SAC is activated, preventing premature anaphase until proper chromosome 10 are established 1. BUB3 also regulates chromosome 10 during oocyte meiosis and is involved in telomere replication and maintenance 1. Clinically, abnormal BUB3 expression is associated with malignancy. Upregulation occurs in various cancers including pancreatic adenocarcinoma, sarcomas, colorectal cancer, and glioblastoma, correlating with poor prognosis and reduced overall and disease-free survival 2 3 4. Conversely, hyperactivation of SAC via YY2-mediated BUB3 transcription suppresses colorectal cancer progression by inducing excessive chr10 instability and mitotic delays 5. BUB3 deficiency is linked to premature aging 1. Recent evidence reveals non-canonical functions: MST1/2 interact with BUB3 to promote pulmonary vascular cell proliferation in pulmonary arterial hypertension 6, and BUB3-mediated deubiquitination of NCAPG enhances gastric cancer immune evasion 7. These findings position BUB3 as a potential therapeutic target with context-dependent roles in disease.