Apoptosis can be induced by certain cytokines including TNF and Fas in the TNF superfamily throμgh interaction with their death domain (DD) containing receptors, TNFR1 and Fas. A member of the TNF receptor family was recently identified and designated DR3 (also called Wal-1, Apo3, TRAMP and LARD). The ligand for this novel death receptor has been defined as TWEAK (also termed Apo3L). Like TNFR1, overexpression of DR3 triggers apoptosis and NF-kB activation. Activation of DR3 results in recruitment of TRADD (a DD containing adapter molecule). TRADD associates with FADD, TRAF2, and RIP to activate the signaling complex for NF-kB activation. DR3 activates apoptosis throμgh TRADD, FADD, and caspase-8. DR3 is highly expressed in the tissues enriched in lymphocytes including peripheral blood leucocytes (PBL), thymus and spleen.