TNF-related weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily (TNFSF) of structurally related cytokines. Like most other members of this family, TWEAK is a cell surface-associated type II transmembrane protein although a smaller, biologically active form can also be generated by cleavage near the cell membrane. TWEAK has multiple biological activities, including stimulation of cell growth and angiogenesis, induction of inflammatory cytokines, in addition to stimulation of apoptosis. The TWEAK signal transduction pathway has not been well established but it appears to signal via TweakR/Fn14 in a manner similar to that described for other TNFSF members that bind receptors lacking death domains.