SLC11A1 encodes a macrophage-specific proton/divalent cation antiporter localized to late endosomal-lysosomal membranes 1. The protein transports bivalent cations, particularly Fe2+ and Mn2+, from the cytosol into acidic compartments, regulating both intracellular metal homeostasis and antimicrobial defense 2. By sequestering essential cofactors required for pathogenic catalases and superoxide dismutases, SLC11A1 simultaneously protects macrophages from oxidative stress while denying these cofactors to intracellular pathogens 1. Genetically, SLC11A1 polymorphisms significantly influence susceptibility to multiple infectious diseases. Meta-analyses demonstrate that variants at D543N, 3'UTR, INT4, and (GT)n loci are associated with increased tuberculosis risk, particularly in Asian populations 34. SLC11A1 polymorphisms also confer susceptibility to cutaneous and visceral leishmaniasis 5, oropharyngeal tularemia 6, and influence Kawasaki disease pathogenesis and BCG hypersensitivity in Korean populations 7. Clinically, SLC11A1 variants represent important genetic biomarkers for infectious disease risk stratification, particularly in non-European populations. The gene's role in macrophage-mediated innate immunity links pathogen susceptibility with inflammatory and autoimmune disease pathways 8, making it a critical locus for understanding host-pathogen interactions.