CASP9 (caspase-9) is a cysteine protease that functions as an initiator caspase in the intrinsic apoptotic pathway 1. Upon apoptotic stimuli, mitochondria release cytochrome c, which binds to Apaf-1 alongside dATP to form the apoptosome complex that recruits and activates caspase-9 1. Activated caspase-9 then cleaves downstream executioner caspases (caspase-3, -6, and -7), initiating the caspase cascade that executes programmed cell death 1. Caspase-9 can also be activated through the extrinsic pathway when caspase-8 cleaves the Bcl-2 family member Bid, triggering mitochondrial cytochrome c release 2. Functionally, caspase-9 is essential for apoptosis during central nervous system development, as homozygous caspase-9 null mice exhibit perinatal lethality with enlarged and malformed cerebra due to reduced developmental apoptosis 1. Therapeutically, caspase-9 has been engineered as an inducible safety switch for T-cell therapies by fusing it to FK506 binding protein domains, enabling selective elimination of transduced cells via dimerizer drug 3. CASP9 polymorphisms show associations with cancer susceptibility; specifically, rs4645981 and rs1052571 variants correlate with increased overall cancer risk 4, while inhibition of miR-182-5p upregulates CASP9 expression to induce apoptosis in breast cancer cells 5.