KIR2DL1 is an inhibitory killer cell immunoglobulin-like receptor expressed on natural killer (NK) cells that binds HLA-C class I molecules (specifically HLA-C group 2 alleles) 1. The receptor delivers inhibitory signals through its long cytoplasmic tail, preventing NK cell activation and cytotoxic degranulation against target cells 2. KIR2DL1 functions in NK cell licensing—the process by which inhibitory receptor engagement confers greater intrinsic responsiveness to subsequent activation signals 1. Structurally, KIR2DL1 contains two immunoglobulin-like domains and a transmembrane region, with expression controlled by complex promoter elements including intermediate regulatory regions that influence gene activation efficiency 3. The receptor exhibits extensive allelic diversity, with multiple variants identified across populations 456. Functionally, KIR2DL1 shares similar licensing capacity with the related inhibitory receptor KIR2DL3, though their relative signal strength does not predict NK cell licensing outcomes 1. Clinically, KIR2DL1 allotypic variants associate with pregnancy outcomes, with KIR2DL1A alleles linked to enhanced NK cell function and increased pre-eclampsia risk 7. Additionally, pathogen-derived ligands like RIFINs from Plasmodium falciparum can bind KIR2DL1 with higher affinity than physiologic HLA-C ligands, suppressing NK cell responses to infection 2.