The protein encoded by this gene is a member of the TNF receptor-associated factor (TRAF) protein family. TRAFs (TNF receptor-associated factors) are a family of multifunctional adaptor proteins that bind to surface receptors and recruit additional proteins to form multiprotein signaling complexes capable of promoting cellular responses. Members of the TRAF family share a common carboxy-terminal "TRAF domain" which mediates interactions with associated proteins; many also contain amino-terminal Zinc/RING finger motifs. The six known TRAFs (TRAF1-6) act as adaptor proteins for a wide range of cell surface receptors and participate in the regulation of cell survival, proliferation, differentiation, and stress responses. TRAF6 plays a critical role in innate and adaptive immunity, bone metabolism, and development of certain tissues including the nervous system. This protein has an amino terminal RING domain which is followed by four zinc-finger motifs, a central coiled-coil region and a highly conserved carboxyl terminal domain, known as the TRAF-C domain. TRAF6 deficiency results in osteopetrosis and defective IL-1, CD40, and LPS signaling as well as defects in neuronal development. Unlike other TRAF family members that mediate signaling through TNF, TRAF6 has unique binding activities that result in signaling responses from the interleukin-1 receptor (IL-1R), toll-like receptor, CD40, RANK, and p75 neurotrophin receptor. TRAF6 associates directly with CD40 and RANK, and indirectly with IL-1R/TLR through IRAK. This leads to activation of NF-kappaB and MAP kinase signaling pathways through downstream association with the TAB/TAK-1 complex. TRAF6 also activates Src family nonreceptor tyrosine kinases leading to Akt activation.