Fas ligand–Fas receptor pathway (FasL–Fas pathway)

The Fas ligand–Fas receptor pathway is a central extrinsic apoptotic signaling system, primarily involving Fas ligand (CD95L) and its receptor, Fas (CD95/APO-1). Fas ligand is a type-II transmembrane protein in the TNF superfamily, mainly expressed on activated cytotoxic T lymphocytes and natural killer cells. Fas receptor is a trimeric membrane-bound receptor featuring an intracellular ‘death domain’ and is expressed on most body cell types but plays a key role in immune regulation. Upon engagement of Fas receptor by Fas ligand, a multi-protein death-inducing signaling complex (DISC) forms, activating caspase-8 and other downstream caspases to execute apoptosis. Non-apoptotic signaling cascades include activation of NF-κB and MAPK, influencing inflammation, proliferation, and differentiation. Dysregulation of Fas/FasL signaling contributes to autoimmune disease, cancer, infection control, and transplant rejection, making both molecules therapeutic and diagnostic targets with notable safety risks related to systemic apoptosis and immune modulation.

Other names

Fas ligand (FasL, CD95L, Apo-1L, apoptosis antigen 1 ligand)Fas receptor (Fas, CD95, APO-1, TNFRSF6)CD178 (for FasL)

Agonistic drugs/antibodies: bind Fas receptor to induce apoptosis in target cells. Antagonistic agents (e.g., decoy receptors, FasL inhibitors): block Fas/FasL interaction to inhibit unwanted apoptosis or inflammation. Recombinant soluble FasL or engineered Fas receptors to modulate cell death or immune function.