The diverse biological effects of the Tumor Necrosis Factor-alpha cytokine are mediated by their binding to specific receptors. TNFRSF1B is a member of a large family of such receptors. This molecule is usually present in the form of cell-surface receptors especially on cells of the immune system, such as the mononuclear cells. The mononuclear cells may also secrete a soluble version of this receptor extracellularly. This condition is especially evident in conditions like rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and other autoimmune disorders, where the soluble receptor is secreted by the mononuclear cells, in order to mop up and block the levels of TNF in the extracellular environment. This action is intended to reduce the activity of the TNF molecules, and inhibit further activation of the mononuclear cells. In fact, in diseases like rheumatoid arthritis, the TNFRSF1B is administered as a medication to control the autoimmune inflammatory reaction.

The TNFRSF1B gene, located on chromosome 1, spans a total length of 42 Kb. The membrane bound protein weighs about 48kDa, and consists of 491 amino acids. The soluble isoform is produced by a proteolytic processing of the membrane isoform. The membrane bound isoform has a very high affinity for TNF-alpha, as well as to the adaptor protein TNF Receptor Associated Factor 2 (TRAF2). The further downstream apoptotic actions of TNF-alpha are, therefore, mediated by TNFRSF1B through TRAF2. The soluble isoform, meanwhile, also has a very high affinity to TNF-alpha. However, it functions antagonistically to the membrane form by blocking TNF-alpha induced apoptosis. Recently, polymorphisms in the TNFRSF1B gene, specifically a single nucleotide polymorphism at position 196 has been shown to be associated with Crohn's disease.