Tumor necrosis factor ligand superfamily member 6 (FASL) (FASL)

Tumor necrosis factor ligand superfamily member 6 (FASL), also known as CD178, is a type II transmembrane protein that serves as a primary initiator of the extrinsic apoptosis pathway [1, 5]. Upon binding to its cognate receptor, Fas (CD95), FASL induces receptor trimerization and the recruitment of adapter proteins like FADD, forming the death-inducing signaling complex (DISC) which activates pro-caspase-8 [2]. This signaling cascade is essential for immune system homeostasis, particularly in the activation-induced cell death (AICD) of T cells and the elimination of virus-infected or transformed cells by cytotoxic T lymphocytes and natural killer cells [1, 3]. In pathological contexts, FASL is often exploited by cancer cells to induce apoptosis in tumor-infiltrating lymphocytes, facilitating immune evasion, while its overactivity is linked to tissue destruction in autoimmune diseases and graft-versus-host disease [3, 5]. Therapeutic interventions include the development of FASL inhibitors like asunercept to treat myelodysplastic syndromes and glioblastoma by preventing premature cell death or immune suppression [4, 6]. Conversely, agonists of the Fas pathway have been explored for cancer therapy, though systemic toxicity, particularly hepatotoxicity, remains a significant challenge [2, 3].

Other names

CD178CD95 ligandFas ligandFASLGTNFSF6APT1LG1Fas antigen ligand

Fas ligand binds to the Fas receptor (CD95), leading to the formation of the death-inducing signaling complex (DISC) and activation of the caspase cascade to initiate extrinsic apoptosis [1, 2].