KLRK1 encodes NKG2D, an activating receptor on natural killer (NK) cells, γδ T cells, and CD8+ T cells that functions in immunosurveillance 1. Upon binding stress-inducible ligands (MICA, MICB, ULBP1-6) displayed on tumor cells and virus-infected cells, KLRK1 stimulates perforin-mediated cytotoxicity and TNF expression through calcium influx signaling 2. On CD8+ T cells, KLRK1 acts as a costimulatory receptor amplifying TCR-mediated activation, while on NK cells it can directly trigger cytotoxicity even in the presence of inhibitory MHC-I signals 1. KLRK1 also participates in NK cell-mediated bone marrow graft rejection and may regulate NK cell differentiation and survival. Clinically, high KLRK1 expression correlates with improved overall and relapse-free survival in lung adenocarcinoma patients 3 and associates with favorable prognosis and increased immune infiltration in head and neck squamous cell carcinoma 4. Conversely, KLRC4-KLRK1 gene polymorphisms influence disease susceptibility: the rs2734565-C allele associates with increased risk and faster onset of antithyroid drug-induced agranulocytosis 5. Additionally, the lncRNA KLRK1-AS1 regulates endothelial progenitor cell wound healing capacity 6.