Apoptosis, or programmed cell death, occurs during normal cellular differentiation and development of multicellular organisms. Apoptosis is induced by certain cytokines including TNF and Fas ligand in the TNF family through their death domain containing receptors, TNFR1 and Fas. A novel death domain containing receptor was recently identified and designated DR4 (for death receptor 4). The ligand for this novel death receptor has been identified and termed TRAIL, which is a new member in the TNF family. DR4 is also called TRAIL receptor-1 (TRAIL-R1). DR4 is expressed in most of human tissues including spleen, peripheral blood leukocytes, small intestine and thymus. Like TNFR1, Fas and DR3, DR4 mediates apoptosis and NF-kappabeta activation in many tissues and cells.