BUB1 is a serine/threonine kinase essential for spindle assembly checkpoint (SAC) signaling and chromosome 2 during mitosis 1. The protein functions through dual mechanisms: it assembles checkpoint proteins at the kinetochore, including CENPF, BUB1B, CENPE, and MAD2L1, and forms a BUB1-BUB3 complex that inhibits APC/C-CDC20 to prevent anaphase until proper chromosome 2 2. BUB1 kinase activity is critical for chromosome 2 and APC/C inhibition 3. Beyond mitotic control, BUB1 regulates sister chr2 cohesion and mediates cell death following chromosome 2, suppressing spontaneous tumorigenesis 4. In disease contexts, BUB1 overexpression correlates with poor prognosis across multiple malignancies. High BUB1 expression drives aneuploidization and tumorigenesis through Aurora B hyperactivation, causing chromosome 2 5. BUB1 is consistently overexpressed in osteosarcoma, liposarcoma, synovial sarcoma, and leiomyosarcoma, with elevated expression predicting reduced overall survival 6. In triple-negative breast cancer, BUB1 inhibition radiosensitizes cells by impairing non-homologous end joining repair of radiation-induced DNA double-strand breaks 7. These findings position BUB1 as both a critical cell cycle regulator and emerging therapeutic target in cancer.