Tumor necrosis factor (TNF) receptor associated factors (TRAFs) are the major signal transducers for the TNF receptor superfamily and the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. TRAF3 was first identified by its interaction with CD40 and the Epstein-Barr virus transforming protein LMP1. Several TRAF3 mRNA splice variants exist and some of these can activate the transcription factor NF-κB. Besides CD40, TRAF3 also interacts with the TRFR superfamily member lymphotoxin-beta receptor (LTbetaR) in association with TRAF2 and the apoptosis inhibitors cIAP1 and Smac. It has been suggested that TRAF3 induces mitochondria-mediated apoptosis upon binding of the TNF family cytokine LIGHT by LTbetaR.