TRAFs (Tumor necrosis factor receptor-associated factors) are cytoplasmic adaptor proteins that associate with tumor necrosis factor receptors (TNFR), thus mediating tumor necrosis factor (TNF) induced signaling. The TRAF family consists of six members (TRAF1-6). TRAF6 possesses several binding motifs in CD40, TRANCE-R and IRAK suggesting a crucial role in TRANCE-R signaling. It is involved in the activation of the anti-apoptotic serine/threonine kinase Akt/PKB through TRANCE-R.6 Due to its specific receptor-binding TRAF-C domain, TRAF6 is the only member of the TRAF family that also participates in signal transduction of the interlukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily.1,7,8 TRAF6 plays a crucial role in adaptive immunity, innate immunity, bone homeostasis, perinatal and postnatal survival, and cytokine signaling. TNF receptor-associated factor 6 (TRAF6) is unique in that it is a signaling adapter molecule common to both families. TRAF6 is important in cytokine production, dendritic cell (DC) maturation, and the T cell stimulatory capacity of DCs in response to TLR and CD40 ligands. It can be activated in the IL-1R/TLR signaling pathway by IL-1 receptor-associated kinase 1 (IRAK-1) or by other TLR adaptor molecules such as TRIF. Also, it has been shown that TRAF6 can interact directly with TNFR family members CD40 and RANK.