CPP32 (also called Yama and apopain) is a member of a growing family of cysteine proteases which includes the interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3. CPP32 has been consistently implicated as a key protease of the ICE/CED-3 family that is activated in response to a variety of death stimuli. Active CPP32 consists of P17 and p12 subunits derived from a 32 kDa pro-enzyme. This activation can be mediated by some ICE-like proteases and the cytotoxic T-cell (CTL) protease granzyme B. Once activated, CPP32 can process some of the other ICE family members and cleaves several cellular proteins in apoptotic cells. Inhibitors of CPP32 and other ICE-like proteases are potent inhibitors of apoptosis and promise to be important therapeutic molecules for the treatment of diseases, such as neurodegenerative and autoimmune disorders, that arise from excessive ell death.