KLRC4-KLRK1 is a natural killer (NK) cell receptor gene located on chromosome 12 that encodes proteins involved in immune surveillance. The gene product functions as a ligand receptor for MICA and participates in NKG2D signaling pathways critical for T cell and NK cell activation 1. KLRC4-KLRK1 polymorphisms significantly influence susceptibility to antithyroid drug (ATD)-induced agranulocytosis in Graves' disease patients; the rs2734565-C allele variant confers 8.36-fold increased risk and accelerates disease onset (median 29 days vs. 57.5 days for non-carriers) 1. Beyond drug toxicity, KLRC4-KLRK1 is recognized as a genetic susceptibility factor for Behçet's disease, a chr12 multisystemic inflammatory disorder 2. In cancer immunology, elevated KLRC4-KLRK1 expression correlates with improved overall survival in breast cancer patients, particularly in specific disease subtypes, suggesting its role in antitumor immune responses 3. Additionally, KLRC4-KLRK1 expression is a highly predictive biomarker for kidney transplant rejection classification, assisting in distinguishing non-rejection from antibody-mediated and T-cell-mediated rejection with 92.1% accuracy 4. These findings indicate KLRC4-KLRK1 functions as both a pharmacogenetic risk factor and an immune checkpoint gene with clinical relevance across autoimmune, inflammatory, and transplantation medicine contexts.