KLRC2 encodes NKG2C, an activating immune receptor expressed on natural killer (NK) cells and cytotoxic lymphocytes that recognizes HLA-E molecules presenting peptide ligands 1. Upon HLA-E binding, KLRC2 transmits intracellular signals through the adapter protein TYROBP/DAP12, triggering NK cell activation and cytotoxic functions 1. KLRC2 plays critical roles in antiviral immunity and adaptive NK cell responses. Notably, KLRC2 deletion alleles are significantly overrepresented in severe COVID-19 patients, particularly those requiring intensive care, indicating that functional NKG2C is protective against SARS-CoV-2 infection 2. The receptor also contributes to transplant immunology; the functional KLRC2 wild-type allele independently associates with microvascular inflammation in antibody-mediated kidney allograft rejection 34. In cancer, KLRC2 expression on tumor cells associates with reduced myeloid-derived suppressor cells and improved responses to PD-1 checkpoint inhibitor therapy in glioblastoma 5. Additionally, KLRC2 participates in coeliac disease pathogenesis through NKG2C/D-mediated epithelial destruction 6. Population studies demonstrate KLRC2 deletion occurs in ~20% of individuals without apparent fitness costs 7, though functionally relevant polymorphisms significantly influence immune-mediated disease severity.