DcR3 is a novel secreted member of the TNFR family. Its closest relative is OPG, to which it shows 31% protein sequence homology. In vitro studies show that DcR3-Fc binds to FasL with an affinity that is comparable to that of Fas-Fc; binding of DcR3-Fc and Fas-Fc to FasL is mutually exclusive, which suggests that DcR3 is a decoy receptor that competes with Fas for FasL binding. DcR3-Fc blocks apoptosis induction by FasL in several cell-based assays. DcR3 binds also to the TNF family member LIGHT, and DcR3-Fc inhibits LIGHT-induced apoptosis in colon cancer cells. The DcR3 gene appears to be amplified frequently in cancer, and DcR3 mRNA is often detectable in malignant tissue. Thus. DcR3 may play a pathologic role in cancer, perhaps through its interaction with FasL and or LIGHT.