FCGR3A encodes Fc gamma receptor IIIa, a low-affinity IgG receptor that plays a crucial role in antibody-dependent cellular cytotoxicity (ADCC) and immune effector functions 12. The receptor primarily mediates NK cell-mediated ADCC through binding to IgG1 and IgG3 antibodies, with binding affinity significantly enhanced by afucosylated antibodies that show increased therapeutic efficacy 2. Functionally important polymorphisms, particularly the F158V variant, create substantial inter-individual variation in receptor activity, with the V158 allele associated with enhanced binding affinity and improved responses to therapeutic antibodies like rituximab and trastuzumab 345. The receptor's interaction depends on a proline sandwich motif that can be disrupted by specific mutations like P329G, completely abolishing FcγR binding 6. Clinically, FCGR3A polymorphisms influence treatment outcomes in cancer immunotherapy and autoimmune diseases, with V158 carriers showing better responses to rituximab therapy 45. Additionally, certain variants including gene duplications and specific genotypes are associated with increased susceptibility to HIV-1 vertical transmission 7. These findings highlight FCGR3A's critical role in therapeutic antibody efficacy and disease susceptibility.