Tumor necrosis factor (TNF) is a multifunctional cytokine that plays a key role in regulating inflammation, immune functions, host defense, and apoptosis (PMID: 16407280). TNF exists in soluble and membrane-bound forms. TNF signals through two distinct cell surface receptors, TNFR1 (TNFRSF1A, CD120a) and TNFR2 (TNFRSF1B, CD120b). Whereas TNFR1 is widely expressed, expression of TNFR2 is limited to cells of the immune system, endothelial cells, and nerve cells (PMID: 22053109). TNFR1, which contains a death domain (DD) within its intracytoplasmic region, is thought to be the key receptor for TNF signaling (PMID: 16407280). This receptor can activate NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor.