-!- Caspase-8 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63). -!- Apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation. -!- Contains two tandem death effector domains (DEDs) in its N-terminal prodomain, which play a role in procaspase activation. -!- Linked to cell surface death receptors such as Fas. -!- When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated. -!- Has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala at the P1' position. -!- Has very broad P4 specificity, tolerating substrates with Asp, Val or Leu in this position. -!- Endogenous substrates for caspase-8 include procaspase-3, the pro- apoptotic Bcl-2 family member Bid, RIP, PAK2 and the caspase-8 activity modulator FLIP(L). -!- Belongs to peptidase family C14.