KLRD1-KLRC1 acts as an immune inhibitory receptor. Key inhibitory receptor on natural killer (NK) cells that regulates their activation and effector functions. Dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells as part of an antigen-driven response to avoid autoimmunity. On intraepithelial CD8-positive gamma-delta regulatory T cells triggers TGFB1 secretion, which in turn limits the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells, distinguishing harmless from pathogenic antigens. In MHC-E-rich tumor microenvironment, acts as an immune inhibitory checkpoint and may contribute to progressive loss of effector functions of NK cells and tumor-specific T cells, a state known as cell exhaustion. Upon MHC-E-peptide binding, transmits intracellular signals through KLRC1 immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules