Fas, also known as APO-1 or CD95, belongs to the death receptor subfamily of the TNF receptor superfamily and is designated TNFRSF6 (1 ‑ 3). Rat Fas cDNA encodes 324 amino acids (aa) that include a 21 aa signal peptide, a 150 aa extracellular domain (ECD) that contains three cysteine-rich TNFR repeats, a 17 aa transmembrane sequence, and a 136 aa cytoplasmic domain containing a death domain (DD), which is required for transducing apoptotic signals (4). Mature rat Fas ECD shares 68% aa sequence identity with mouse Fas, and 56 ‑ 58% with human, feline, bovine and porcine Fas. A 114 aa potential rat Fas isoform contains an alternate start site at aa 211, thus lacking all three TNFR repeats (5). The Fas ligand (FasL, TNFSF6) is a type II transmembrane protein of the TNF family that can be expressed on activated T-lymphocytes, NK cells and cells in immune privileged sites, or shed in soluble form (2). Engagement of FAS induces oligomerization of preformed Fas trimers (1, 2). The activated receptor recruits the adaptor molecule FADD to form the Death-Inducing Signaling Complex (DISC). Upon activation, caspases in the DISC initiate the apoptotic signaling cascade (6). Fas is prominent in epithelial cells, hepatocytes, activated mature lymphocytes, virus-transformed lymphocytes and tumor cells. It is an essential mediator in the activation-induced death of T lymphocytes that terminates the immune reaction (1, 2, 7). In immune-privileged tissues, infiltrating Fas-bearing lymphocytes and inflammatory cells are killed by FasL engagement (8). Both humans and mice with genetic defects in Fas accumulate abnormal lymphocytes and develop systemic autoimmunity (1 ‑ 3). The Fas pathway also appears to cross-communicate with the BIM (mitochondrial/intrinsic) apoptosis pathway (1).