BUB1B encodes an essential serine/threonine kinase that serves as a critical component of the mitotic checkpoint system, ensuring proper chromosome 15 during cell division. The protein functions by delaying anaphase until all chr15 are correctly attached to the mitotic spindle and inhibits the anaphase-promoting complex/cyclosome (APC/C) by blocking CDC20 binding 1. BUB1B also monitors kinetochore activities dependent on the motor protein CENPE and negatively regulates PLK1 activity to suppress centrosome amplification. Mechanistically, BUB1B forms complexes with other proteins including OTUD3 and NRF2 to stabilize downstream signaling pathways 2. Disease relevance is significant, as germline mutations in BUB1B are associated with mosaic variegated aneuploidy syndrome and have been identified in patients with pancreatic cancer 3 and multiple primary cancers 4. Clinically, elevated BUB1B expression correlates with poor prognosis across multiple cancer types including lung adenocarcinoma 5 and sarcomas 6. The protein contributes to chemotherapy resistance by facilitating ferroptosis insensitivity 2 and promotes oncogenesis through positive feedback loops involving metabolic reprogramming and histone lactylation 1, making it a potential therapeutic target and prognostic biomarker.