Natural cytotoxicity triggering receptor 3 ligand 1(B7-H6) is a glycosylated member of the B7 family of immune costimulatory proteins. Mature human B7-H6 consists of a 238 amino acid (aa) extracellular domain (ECD) that contains one Ig-like V domain and one Ig-like C1 domain, a 21 aa transmembrane segment, and a 171 aa cytoplasmic domain that contains one ITIM, one SH2, and one SH3 motif. Both of the Ig-like domains carry N-linked glycosylation. The Ig-like V domain mediates 1:1 stoichiometric binding of B7-H6 to NKp30 expressed on NK cells. It does not show binding to NKp44, NKp46, or NKG2D. Ligation of NKp30 by B7-H6 induces NK cell activation and target cell cytolysis. B7-H6 is expressed on a wide range of hematopoietic, carcinoma, and melanoma tumor cells, which is consistent with the detection of NKp30 binding sites on many tumors.