CASP2 (caspase 2) is a multifunctional enzyme that plays critical roles beyond traditional apoptosis. The protein exhibits novel deubiquitinase activity, accumulating in ubiquitin-positive condensates called ubstressomes where it removes excessive ubiquitin chains from misfolded proteins to maintain cellular protein quality control 1. In apoptotic signaling, CASP2 functions through the PIDDosome complex to eliminate cells with extra centrosomes, preventing pathogenic polyploidization by cleaving BID and activating mitochondrial apoptosis pathways 2. The enzyme also regulates innate immunity by cleaving key antiviral proteins including cGAS, MAVS, and IRF3, thereby preventing cytokine overproduction during viral infections 3. In the nervous system, CASP2 suppression combined with CASP6 inhibition promotes retinal ganglion cell survival and axon regeneration through CNTF-mediated JAK/STAT signaling 4. CASP2 is implicated in neurodegenerative diseases, with selective inhibitors showing therapeutic potential in Alzheimer's disease by preventing synapse loss and in NASH by blocking SREBP2 activation 5. The protein uniquely localizes to the nucleus constitutively, though its nuclear function remains unclear 6.