As part of the down-regulation of the immune response, activated T lymphocytes up-regulate Fas expression and activated B and T lymphocytes up-regulate expression of Fas-ligand. Fas and Fas-ligand interact through the Fas-activating death domain (FADD) to trigger the caspase cascade, leading to proteolysis, DNA degradation, and apoptosis. Germline mutations have been described in ALPS in FAS, Fas-ligand, and caspase 10. Somatic mutations have been identified only in FAS; however, they could be found in other genes with future study. Professional illustration by Sue Seif (used with permission).