Fasligand

FasLigand, commonly called FasL or CD95L, is a type II transmembrane protein in the tumor necrosis factor (TNF) superfamily. It binds to the Fas receptor (CD95) on target cells to initiate programmed cell death (apoptosis). In humans, FasL is encoded by the FASLG gene.

FasL exists in two main forms: a membrane-bound ligand responsible for most cytotoxic interactions, and a soluble form produced by proteolytic shedding. The membrane-bound form engages Fas on adjacent cells to trigger signaling, while soluble FasL can modulate signaling in certain contexts and may have distinct biological effects.

Expression of FasL is highest on activated cytotoxic CD8+ T cells and natural killer (NK) cells, but it is also found on other immune and non-immune cells such as dendritic cells, macrophages, and endothelial cells. Its expression is regulated by immune activation and cytokine signals, enabling it to participate in immune surveillance and regulation.

Mechanistically, FasL binding to Fas promotes receptor trimerization and assembly of the death-inducing signaling complex (DISC), recruiting FADD and initiating a caspase cascade (caspase-8 and downstream effector caspases like caspase-3) that leads to apoptosis. In some cell types, Fas signaling can activate non-apoptotic pathways (for example NF-κB or MAPK) and influence inflammation or cell survival depending on the cellular context.

Clinical relevance of FasL signaling includes roles in immune homeostasis, immune privilege, and cancer immune evasion. Dysregulation of FasL or its receptor can contribute to autoimmune or lymphoproliferative disorders in rare cases. Therapeutic applications and research have explored soluble or recombinant FasL, but systemic use is limited by toxicity and off-target effects.