FAS (also known as APO-1 or CD95) is a member of the tumor necrosis factor receptor (TNF-R) family that contains an intracellular 'death domain' and can trigger apoptosis. Its physiological ligand, FASL (CD95L), is a member of the TNF cytokine family. Studies in mice and humans have shown that FAS and FASL play critical roles in the immune system, particularly in the killing of pathogen-infected target cells and the death of no longer needed, potentially harmful, or autoreactive lymphocytes. FASL-FAS signaling triggers apoptosis through the recruitment and activation of caspase-8 via the FADD adaptor protein. In certain cells like hepatocytes, FAS-induced apoptosis requires proteolytic activation of BID. FAS signaling also plays non-apoptotic roles in cellular activation, differentiation, and proliferation. FASL-FAS signaling is critical for immune system control and tumor suppression, as demonstrated by the increased lymphoma predisposition in FAS- or FASL-deficient mice. FASL expressed on activated T cells or NK cells contributes to their ability to kill target cells. Abnormally increased FASL-mediated killing of healthy cells has been implicated in certain immunopathological states. Pharmacological modulation of FASL-FAS signaling may be a useful strategy for therapeutic intervention, but caution is needed due to potential side effects. Understanding FASL-FAS signaling may allow for more subtle intervention strategies. FASL-FAS signaling induces apoptosis through the formation of a death-inducing signaling complex (DISC), involving caspase-8, FADD, and c-FLIP. BID is a critical substrate of caspase-8, and its proteolysis leads to mitochondrial apoptosis. FASL-FAS signaling is essential for the killing of antigen-activated lymphocytes during immune responses. FASL-FAS signaling also plays a role in the control of lymphocyte homeostasis, with FAS and FASL being critical for the deletion of autoreactive T and B cells. FASL-FAS signaling is involved in the pathogenesis of autoimmune diseases such as SLE and type I diabetes. FASL-FAS signaling also has non-apoptotic functions, including the induction of cellular activation, proliferation, and differentiation. FASL-FAS signaling is essential for the control of immune responses and the prevention of autoimmunity. The role of FASL-FAS signaling in the immune system is complex and multifaceted, with implications for both normal and pathological immune responses.FAS (also known as APO-1 or CD95) is a member of the tumor necrosis factor receptor (TNF-R) family that contains an intracellular 'death domain' and can trigger apoptosis. Its physiological ligand, FASL (CD95L), is a member of the TNF cytokine family. Studies in mice and humans have shown that FAS and FASL play critical roles in the immune system, particularly in the killing of pathogen-infected target cells and the death of no longer needed, potentially harmful, or autoreactive lymphocytes. FASL-FAS signaling triggers apoptosis through the recruitment and activation of caspase-8 via the FADD adaptor protein. In certain cells like hepatocytes, FAS-induced apoptosis requires proteolytic activation of BID. FAS signaling also plays non-apoptotic roles in cellular activation, differentiation, and proliferation. FASL-FAS signaling is critical for immune system control and tumor suppression, as demonstrated by the increased lymphoma predisposition in FAS- or FASL-deficient mice. FASL expressed on activated T cells or NK cells contributes to their ability to kill target cells. Abnormally increased FASL-mediated killing of healthy cells has been implicated in certain immunopathological states. Pharmacological modulation of FASL-FAS signaling may be a useful strategy for therapeutic intervention, but caution is needed due to potential side effects. Understanding FASL-FAS signaling may allow for more subtle intervention strategies. FASL-FAS signaling induces apoptosis through the formation of a death-inducing signaling complex (DISC), involving caspase-8, FADD, and c-FLIP. BID is a critical substrate of caspase-8, and its proteolysis leads to mitochondrial apoptosis. FASL-FAS signaling is essential for the killing of antigen-activated lymphocytes during immune responses. FASL-FAS signaling also plays a role in the control of lymphocyte homeostasis, with FAS and FASL being critical for the deletion of autoreactive T and B cells. FASL-FAS signaling is involved in the pathogenesis of autoimmune diseases such as SLE and type I diabetes. FASL-FAS signaling also has non-apoptotic functions, including the induction of cellular activation, proliferation, and differentiation. FASL-FAS signaling is essential for the control of immune responses and the prevention of autoimmunity. The role of FASL-FAS signaling in the immune system is complex and multifaceted, with implications for both normal and pathological immune responses.