The KLRK1 gene encodes NKG2D, a C-type lectin-like activating receptor predominantly expressed on natural killer (NK) cells and subsets of T cells, including CD8+ cytotoxic T cells and γδ T cells. NKG2D plays a critical role in innate and adaptive immunity by recognizing stress-induced ligands (e.g., MICA, MICB, ULBP1-6) displayed on infected, transformed, or damaged cells. This interaction triggers cytotoxic responses and cytokine production, enabling immune surveillance against pathogens and malignancies. KLRK1 antibodies are tools designed to target the NKG2D protein for research or therapeutic purposes. In research, they are used to study receptor-ligand interactions, immune cell activation, and tumor immune evasion mechanisms. Therapeutically, NKG2D-targeting antibodies have been explored to modulate immune responses—either blocking NKG2D to suppress autoimmune or inflammatory conditions or enhancing NK/T cell cytotoxicity in cancer immunotherapy. However, clinical applications face challenges, such as balancing efficacy with potential off-target effects due to the receptor's broad ligand specificity. Recent studies also investigate KLRK1 antibodies in biomarker discovery, given the correlation between NKG2D ligand expression and disease progression in cancers or viral infections. Overall, KLRK1 antibodies serve as pivotal reagents for dissecting immune pathways and developing immunotherapies.