Killer cell immunoglobulin-like receptor 3DL2 is a protein that in humans is encoded by the KIR3DL2 gene. The protein IGSF8 (Immunoglobulin superfamily member 8) has been identified as a binding partner of the KIR3DL2 receptor. Binding of IGSF8 to KIR3DL2 expressed on the surface of natural killer (NK) cells acts as an immune checkpoint that inhibits cytotoxic activity and cell killing by NK cells. KIR3DL2 is highly expressed on both NK cells and γδ T cells (a subtype of non-MHC-I restricted T cells). Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes.