The A4GALT antibody is associated with the P1PK blood group system, which is governed by the A4GALT gene located on chromosome 22. This gene encodes α-1.4-galactosyltransferase, an enzyme responsible for synthesizing the P1 and Pk antigens on red blood cells (RBCs) and other tissues. Antibodies targeting these antigens, such as anti-P1 and anti-PP1Pk, are clinically significant in transfusion medicine and pregnancy. Anti-P1 is a naturally occurring IgM antibody commonly found in individuals with the P2 phenotype (lacking P1 antigen). While often benign, it can occasionally cause hemolytic transfusion reactions or complicate serologic testing. In contrast, anti-PP1Pk (historically termed anti-Tja) is a rare but potent IgG/IgM mixture targeting both P1 and Pk antigens. It is linked to severe hemolytic disease of the fetus and newborn (HDFN) and acute hemolytic transfusion reactions, particularly in individuals with the rare p phenotype (lacking all P system antigens due to A4GALT mutations). Detection of these antibodies relies on agglutination assays and molecular typing. Recent studies also highlight A4GALT's pleiotropic roles beyond blood grouping, including potential associations with cancer progression and bacterial adhesion. Understanding A4GALT antibodies remains critical for safe transfusion practices and managing alloimmunization risks.