The ABO gene encodes a glycosyltransferase that catalyzes the transfer of either N-acetylgalactosamine or galactose in an alpha-1,3 linkage to H antigens on cell surfaces, thereby establishing the A and B blood group antigenic structures. The enzyme localizes to the Golgi apparatus and operates as a manganese-dependent transferase on glycoproteins and glycolipids. ABO variants determine blood group phenotypes with profound implications for transfusion medicine, organ transplantation compatibility, and disease susceptibility. Polymorphisms at this locus influence not only red blood cell serotype but also plasma levels of von Willebrand factor and other hemostatic factors, affecting thrombotic and hemorrhagic risk. Blood group incompatibility remains a critical barrier to successful allogeneic transplantation, making ABO typing and crossmatching essential clinical safeguards. The gene's role in defining immunologically distinct cell surface signatures makes it foundational to transfusion safety and transplant immunology.