TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines and induces apoptosis in a wide variety of cells. Using a combination of PCR and library screening, the authors isolated cDNAs corresponding to the TRAILR2 coding region. The predicted 440-amino acid protein contains a putative signal peptide, 2 cysteine-rich pseudorepeats characteristic of TNF receptor (TNFR) family members, a transmembrane domain, and an intracellular death domain. The death domain of TRAILR2 shares 30% identity with that of TNFR1. Overall, the TRAIL receptors TRAILR2 and TRAILR1 (DR4) are 58% identical. Northern blot analysis indicated that TRAILR2 was expressed as a 4.4-kb mRNA in all tissues tested, with the highest levels of expression in peripheral blood lymphocytes, spleen, and ovary.