CD337, also known as NKp30, is a 30-kDa transmembrane glycoprotein which is a NK-specific triggering receptor involved in non-MHC-restricted natural cytotoxicity. NKp30 is strictly expressed by all resting and activated NK cells including the minor CD3–CD56brightCD16– subset. With NKp46 and NKp44 it is one of the three identified NK natural cytotoxicity receptors (NCR). Its surface expression parallels that of NKp46. NKp46dull NK cells are also characterised by a NKp30dull phenotype while NKp46bright NK cells show a NKp30bright phenotype. The NKp30bright or NKp30dull phenotypes are correlated with high or low cytotoxicity, respectively. CD337 is a member of the immunoglobulin superfamily characterized by a single extracellular V-type Ig-like domain. It is associated with a homodimer of ITAM motif-containing CD3ζ adaptor proteins. These adaptor proteins are not necessary for surface expression of NKp30, but are necessary for signal transduction. In redirected killing assays, Z25-mediated cross linking of NKp30 induces strong NK cell activation. Conversely, Z25-mediated masking of NKp30 inhibits NK cytotoxicity against target cells. More importantly, CD337 represents the major receptor in induced NK-mediated killing of certain target cells, the lysis of which is largely NKp46 / NKp44 independent. Although the CD337 ligand is unknown, studies report NKp30-mediated lysis of immature dendritic cells (iDC). These findings suggest that DCs express one or more unidentified ligands for CD337.