A unique family of cysteine proteases has been described that differs in sequence, structure and substrate specificity from any previously described protease family. This family, Ced-3/caspase-1, is composed of caspase-1, caspase-2, caspase-3, caspase-4, caspase-6 and caspase-7 (also designated Mch3, ICE-LAP3 or CMH-1), caspase-9, caspase-10, caspase-14, and caspase-5/caspase-12. Ced-3/caspase-1 family members function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. Caspase-5 (also designated TY or ICErelIII) can cleave its own precursor, an activity that requires the cysteine 245 residue. The mouse homolog of caspase-5 is designated caspase-12. Frameshift mutations in caspase-5 have been identified in MMP tumors of the endometrium, colon and stomach, indicating that caspase-5 may be a new target gene in the microsatellite mutator pathway for cancer.