Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors. TRAIL/Apo2L is a new member of the TNF family and induces apoptosis of a variety of tumor cell lines. DR4 and DR5 are the recently identified functional receptors for TRAIL. Two decoy receptors for TRAIL have been identified and designated DcR1/TRID/TRAIL-R3/LIT and DcR2/TRAIL-R4/TRUNDD. DcR1 has extracellular TRAIL-binding domain but lacks intracellular signaling domain. It is a glycophospholipid-anchored cell surface protein. DcR1 transcripts were expressed in many normal human tissues but not in most cancer cell lines. Overexpression of DcR1 did not induce apoptosis, but attenuated TRAIL-induced apoptosis.