TNF, as also known as TNF-alpha, or cachectin, is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. It is expressed as a 26 kDa membrane bound protein and is then cleaved by TNF-alpha converting enzyme (TACE) to release the soluble 17 kDa monomer, which forms homotrimers in circulation. It is produced chiefly by activated macrophages, although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. rat and human TNF-alpha share 79% amino acid sequence identity. Unlike human TNF-alpha, the rat form is glycosylated. In rat deficiency of this gene is associated with defects in response to bacterial infection, with defects in forming organized follicular dendritic cell networks and germinal centers, and with a lack of primary B cell follicles.