TNF RI is also known as the p60 or p55 TNFR) and TNF RII (the p75 or p80 TNFR) are two distinct type I transmembrane glycoproteins that bind TNF with highaffinity.Both RI and RII are prototypic members of the TNF receptor superfamily and have been designated TNFRSF1A and TNFRSF1B, respectively. Human TNF RII cDNA encodes a 461 amino acid (aa) residue precursor protein with a 22 aa putative signal peptide, a 235 aa extracellular domain, a 20 aa transmembrane domain and a 174 aa cytoplasmic domain. TNFRII is expressed in fetal brain. The protein is produced naturally as a soluble form (sTNFRII). The soluble receptor inhibits TNFα action by competing with cell surface receptors in binding TNFα, thereby blocking its biologic effects. TNFRII is strongly expressed at the cartilage–pannus junction, and plays a major role in a subset of families with multiple cases of rheumatoid arthritis (RA). Further, high plasma levels of sTNFRII were significantly associated with increased incidence of coronary heart disease, independent of established cardiovascular risk factors, and seems to be useful for monitoring the inflammatory activity of sarcoidosis.