CASP6 encodes caspase-6, an execution-phase cysteine protease that plays critical roles in apoptosis and inflammatory cell death pathways. As a key executor of programmed cell death, CASP6 functions through proteolytic cleavage of target proteins and can interact with other caspases and cell death machinery 1. The protein is involved in multiple cell death modalities including pyroptosis, apoptosis, and PANoptosis - a recently characterized form involving simultaneous activation of multiple death pathways 23. CASP6 serves as a downstream effector in various signaling cascades, including FXR-mediated pathways where it promotes beta cell apoptosis during development 4. In cancer contexts, CASP6 expression correlates with tumor progression and treatment response, with higher expression associated with poor prognosis in glioma patients but potentially better response to certain therapies 5. Somatic mutations in CASP6 have been identified in colorectal and gastric carcinomas, though at low frequencies 6. The protein also contributes to drug resistance mechanisms in leukemia through suppression by transcription factors like CEBPB 7. Therapeutically, combined inhibition of CASP6 with other caspases can promote neuronal survival and axon regeneration through CNTF-mediated signaling pathways 1.