HLA-C is a major histocompatibility complex class I molecule that functions as a critical regulator of adaptive and innate immune responses. As an antigen-presenting molecule, HLA-C presents peptide antigens to CD8+ T cells, triggering cytotoxic responses against pathogens such as CMV 1. HLA-C also serves as a ligand for killer immunoglobulin-like receptors (KIR) on natural killer cells, providing inhibitory signals that fine-tune NK cell lytic activity through cis interactions 2. This tuning mechanism is evolutionarily conserved and controls NK cell activation based on HLA-C expression levels and allelic variants. HLA-C polymorphisms have significant disease relevance. Specific HLA-C/KIR allele combinations increase susceptibility to HPV infection and cervical lesions 3. In HIV-1 transmission, HLA-C*15 acts as a protective allele while HLA-C*07 increases transmission risk 4. Additionally, pathogens including varicella-zoster virus exploit HLA-C by sequestering it to the Golgi complex to evade immune presentation 5. HLA-C/KIR interactions also influence reproductive outcomes, where specific combinations affect NK cell function at the maternal-fetal interface 6. Clinically, HLA-C typing may serve as a risk marker for HPV-related disease progression and could inform population-specific vaccine strategies against HIV-1 4. Understanding HLA-C diversity and expression patterns is essential for predicting infectious disease outcomes and designing immunotherapeutic interventions.