FASCD95

FasCD95, commonly known as Fas or CD95, is a cell surface receptor that mediates a form of programmed cell death known as apoptosis. It is a member of the tumor necrosis factor receptor (TNFR) superfamily and is encoded by the FAS gene, located on chromosome 10 in humans. The Fas protein is a type I transmembrane receptor with an extracellular domain containing cysteine-rich repeats, a single transmembrane segment, and an intracellular death domain that participates in signaling.

The physiological ligand for Fas is Fas ligand (FasL, CD95L), which is primarily expressed as a membrane-bound protein on activated cytotoxic T cells and other cell types. Engagement of Fas by FasL promotes receptor trimerization and the assembly of the death-inducing signaling complex (DISC), consisting of FADD adaptor protein and procaspase-8 or -10. Activation of initiator caspases triggers a caspase cascade, leading to downstream effector caspases and apoptosis. In some cells (type II), caspase-8 also activates the mitochondrial (intrinsic) pathway via Bid cleavage, amplifying the apoptotic signal.

Fas/CD95 signaling plays key roles in development, immune system regulation, and peripheral tolerance, including deletion of autoreactive lymphocytes. Dysregulation or mutation of FAS can lead to autoimmune lymphoproliferative syndrome (ALPS) and contribute to cancer immune evasion. Conversely, strategies to modulate Fas signaling have been explored for therapeutic purposes, though clinical applications face challenges such as toxicity. Soluble Fas (sFas) can act as a decoy receptor, inhibiting FasL binding and apoptosis. Overall, FasCD95 is a central component of apoptosis signaling with broad relevance to physiology and disease.