Tumor necrosis factor (TNF) induced signaling is mediated through association of TNF receptor (TNFR) with adaptor proteins, such as TNF receptor associated proteins (TRAFs). TRAFs form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily (e.g. RANK, CD30, CD40, etc.) and the interleukin-1 receptor. The carboxy-terminal region of TRAFs is required for self-association and interaction with receptor cytoplasmic domains following ligand-induced oligomerization. Recent molecular cloning studies have lead to identification of six TRAFs (TRAF1-TRAF6) (1-4). TRAF2 is a 502-amino acid protein. Mutagenic studies suggest that the N-terminal RING finger and two adjacent zinc fingers of TRAF2 are required for NF-κ,B activation, where as interaction with TNFR is mediated through C-terminus domain (5,6). Distinct domains in the N- and -C termini are also required for association with TRAF1 and protein kinase receptor interacting protein (RIP). TRAF2 is involved in cellular resistant to TNF-induced apoptosis. TRAF-2 deficient mice appeared normal at birth, however, they die prematurely, probably due to atrophy of thymus, spleen, muscle mass and lack of TRAF-2's cytoprotective role.