Publisher Summary Most cell types express both of the two receptors for TNF. CD120a is constitutively expressed at a low level, and CD 120b expression is inducible. Both receptors are members of the TNFR superfamily, and contain four cysteine-rich repeats, but are <25% identical to each other, that is, no more similar to each other than to the other members of this family of receptors. The structure of a complex between the trimeric lymphotoxin α (LTa) and three molecules of the extracellular domain of CD120a has been determined by X-ray crystallography. The structure of the extracellular domain of CD120a has also been determined in the absence of ligand, and it forms a dimer, but it is not known whether this occurs at the membrane. CD120a contains a “death domain” within the cytoplasmic region. CD120a and CD120b are receptors for both TNFα and TNFβ (LTα) that are cytokines produced primarily by macrophages/monocytes, activated T cells, and NK cells in response to bacterial, viral, and parasitic infections. TNF mediates a wide variety of effects including tumor necrosis, anorexia, fever, induction of other cytokines, cell differentiation, and apoptosis. The most effective cell killing occurs when membrane bound TNF cross-links both CD120a and CD120b.