Caspases are a family of cysteine proteases with roles in cytokine matur-ation or apoptosis. Caspase-2 was the first pro-apoptotic caspase identified, but its functions in apoptotic signal transduction are still being elucidated. This study examined the regulation of the activity of caspase-2 using recombinant proteins and a yeast-based system. Our data suggest that for human caspase-2 to be active its large and small subunits must be separ-ated. For maximal activity its prodomain must also be removed