FAS-Associated Death Domain Protein (FADD) Protein

Background

FADD is an adaptor protein critical for death receptor-mediated apoptosis and immune signaling. It binds to death receptors like FAS (CD95), TNFR1, and TRAIL-R through its death domain (DD), facilitating the recruitment of caspase-8 to form the death-inducing signaling complex (DISC). This activates caspase cascades, leading to programmed cell death. FADD also participates in necroptosis, a caspase-independent cell death pathway, by interacting with receptor-interacting proteins (RIPK1 and RIPK3). Beyond cell death, FADD regulates T-cell proliferation, innate immune signaling, and NF-κB activation. Dysregulation of FADD is implicated in cancers, autoimmune diseases, and viral infections, where it affects apoptosis resistance and inflammation. Knockout studies reveal its essential role in embryonic development, immune homeostasis, and T-cell activation, emphasizing its dual function in cell survival and death signaling.