The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family consists of six mammalian members, and is shown to participate in signal transduction of a large number of receptor families including TNF receptor family (TNFR) and Toll-like receptors-interleukin-1 receptors (TLR-IL-1R) family. Upon receptor activation, TRAFs are directly or indirectly recruited to the intracellular domains of these receptors. They subsequently engage other signaling proteins to activate inhibitor of kappaB kinase (IKK) complex, TRAF family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1) and inducible I kappaB kinase (IKK-i) (also known as IKKepsilon), ultimately leading to activation of transcription factors such as NF-kappaB and interferon-regulatory factor (IRF) to induce immune and inflammatory responses.