Caspases are a family of cysteine proteases that are key mediators of programmed cell death or apoptosis. The precursor forms of caspases are composed of a prodomain, and large and small catalytic subunits. The active forms of caspases are generated by several stimuli including ligand-receptor interactions, growth factor deprivation, and inhibitors of cellular functions. All known caspases require cleavage adjacent to aspartates to liberate one large and one small subunit, which associate into a alpha2beta2 tetramer to form the active enzyme. To date, approximately 14 caspases have been identified in mammals. Caspases can be divided into three groups based upon structural differences and substrate preferences. These include apoptotic initiators (caspase-2, -8, -9, and -10), apoptotic executioners (caspase-3, -6, and -7), and cytokine processors (caspase-1, -4, -5, -13, murine caspase-11, -12, and -14). Caspase-12 has been cloned from the mouse, and based upon sequence homology to other murine caspases (mCASP) can be divided into a subfamily including mCASP1 and -11. The tissue distribution of mCASP-12 was examined by Northern blot analysis and found to be expressed in most tissues, but was highest in skeletal, muscle, and lung tissue. Caspase-12 has been reported to be activated when the endoplasmic reticulum (ER) undergoes stress, and a participant in ER stress-induced apoptosis pathway. Mice deficient for caspase-12 do not undergo ER stress-induced apoptosis, but their cells are capable of undergoing programmed cell death induced by other stimuli. Murine caspase-12 migrates at ~55 kDa in SDS-PAGE. The antibodies recognize human, mouse, and rat caspase-12. A synthetic peptide corresponding to amino acids 2-17 of murine caspase-12 was used as the immunogen.