CD27 is a 50 kDa member of the tumor necrosis factor (TNF) receptor superfamily that includes CD40 and CD30. The TNF superfamily members are known for the regulation of cell proliferation and death. In contrast to the expression of other TNFR/TNF family members, expression of CD27 and its ligand CD70 is predominantly confined to lymphocytes. High expression levels of CD27 appear to be dependent on proper ligation of antigen receptors. CD70 expression requires additional co-stimulatory and/or pro-inflammatory signals. CD27 is expressed as a disulfide-linked homodimer on mature thymocytes, peripheral blood T cells and a subpopulation of B cells. Activation of T cells via TCR-CD3 complex results in upregulation of CD27 expression on the plasma membrane as well as in the release of its soluble 28-32 kDa form, sCD27, detected in the plasma, urine or spinal fluid. Soluble CD27 is an important prognostic marker of acute and chronic B cell malignancies. RgpA, a cystein proteinase, although activating T cells through the protease-activated receptors (PARs), degradates CD27 and counteracts T cell activation mediated by CD27 and its ligand CD70. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. Diseases associated with CD27 dysfunction include Lymphoproliferative Syndrome 2 and Autosomal Recessive Lymphoproliferative Syndrome.