Caspase-8, also known as MCH5, FLICA and MACH alpha 1, is a 28 kDa member of the peptidase C14A family of enzymes. It is widely expressed and is considered an initiating caspase for the apoptotic cascade. Caspase-8 acts on a wide variety of substrates including Pro-Caspases-3, -4, -6, -7, -9 and -10, c-FLIPL and Pro-Caspaseâ8 itself. Caspase-8 is recruited to the death-inducing signaling complex (DISC) that forms around the death domains of the oligomerized receptors. Multiple rounds of cleavage generate Caspase-8 p10 and p18 which heterodimerize and then associate into the active tetrameric enzyme containing two p10 and two p18 subunits.