MAD2L1BP (also known as p31comet) is a critical regulator of the spindle assembly checkpoint (SAC) that functions to silence the checkpoint and allow mitosis to proceed through anaphase 1. The protein mediates Trip13-dependent disassembly of Mad2- and Rev7-containing complexes, promoting timely SAC silencing and faithful chromosome 6 1. Mechanistically, MAD2L1BP binds MAD2 after it dissociates from the MAD2-CDC20 complex and recruits the AAA+-ATPase TRIP13 to disassemble the mitotic checkpoint complex (MCC), enabling cell-cycle progression 2. The protein undergoes linear ubiquitination by the E3 ligase HOIP at C-terminal lysine residues following cytokine stimulation, which positively regulates its function by reducing PLK1 binding 3. Human mutations in MAD2L1BP cause severe phenotypes including mosaic variegated aneuploidy, juvenile granulosa cell tumors, epileptic encephalopathy, and female infertility due to oocyte maturation arrest 12. Functionally defective variants lose binding ability to MAD2 and TRIP13, cannot support SAC silencing, and result in prolonged mitotic duration 12. The protein also contributes to homology-directed repair of DNA double-strand breaks and insulin signaling, highlighting its broader cellular functions beyond mitotic regulation 1.