TNF-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand and TNFSF10, is a type II transmembrane protein with a carboxy-terminal extracellular domain that exhibits homology to other TNF superfamily members.
TRAIL binds at least five different receptors: TRAIL R1 (DR4), R2 (DR5), R3 (DcR1), R4 (DcR2), and osteoprotegerin (OPG). TRAIL receptors all exhibit cysteine-rich repeats characteristic of the TNF receptor superfamily. TRAIL R1 and R2 are type 1 transmembrane proteins with intracellular death domains (DD) and, subsequently, have the ability to mediate TRAIL-induced apoptosis. The remaining receptors are decoys that may regulate TRAIL activity by competing for binding sites with TRAIL R1 and R2. TRAIL R3 is membrane-associated via GPI linkage. TRAIL R4 is a type 1 transmembrane receptor, but exhibits a truncated cytoplasmic domain. Like the active receptors TRAIL R1 and R2, OPG has a DD motif but is a soluble protein.