TRAFs (TNF receptor associated proteins) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily 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). Recently it has been shown that TRANCE/OPGL activates the antiapoptotic serine/threonine kinase Akt/PKB throμgh a signaling complex involving c-Src and TRAF6. Mice deficient in TRAF6 are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Like TRAF2 and TRAF3, TRAF6 is also essential for perinatal and postnatal survival. These findings establish diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.