Killer cell immunoglobulin-like receptor 2DL1(KIR2DL1), which belongs to the immunoglobulin superfamily, is an inhibitory receptor of NK cells. Regulation of NK cell activity is mediated through killer-cell immunoglobulin-like receptors (KIR) ability to recognize human leukocyte antigen (HLA) class I molecules as ligands. Interaction of KIR and HLA is implicated in viral infections, autoimmunity, and reproduction and there is growing evidence of the coevolution of these two independently segregating gene families. Association of KIR2DL1 with β-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated downstream inhibitory signaling.