Caspase-2 (CASP2) (CASP2)

Caspase-2 (CASP2) is a highly conserved cysteine-aspartic acid protease that functions as an initiator of apoptosis, uniquely positioned between the intrinsic and extrinsic cell death pathways (UniProt P42575). Unlike other initiator caspases, Caspase-2 is primarily activated by the PIDDosome complex—comprising PIDD1 and RAIDD—in response to genotoxic stress, DNA damage, or metabolic disturbances, rather than direct death receptor ligation (Bouchier-Hayes & Green, 2012). It plays a pivotal role in the progression of non-alcoholic steatohepatitis (NASH) by promoting hepatocyte death and has been implicated in the synaptic loss associated with Alzheimer's disease (Machado et al., 2015; Zhao et al., 2016). In oncology, Caspase-2 can act as a tumor suppressor by eliminating damaged cells, though its role is context-dependent. Therapeutic strategies involving Caspase-2 focus on small-molecule inhibitors to treat chronic inflammatory and neurodegenerative conditions, or activators to overcome apoptosis resistance in cancer (NIH PubChem). Current clinical efforts, such as those involving the pan-caspase inhibitor Emricasan, highlight the potential of modulating this pathway to treat liver fibrosis and other cell-death-mediated pathologies.

Other names

Cysteine-aspartic acid protease 2ICH-1NEDD2CASP-2

Inhibition of the catalytic activity of Caspase-2 to prevent apoptosis and inflammatory signaling.