A3GALT2 (alpha 1,3-galactosyltransferase 2) encodes a glycosyltransferase that synthesizes the galactose-alpha(1,3)-galactose epitope on isoglobotrihexosylceramide (iGb3) by catalyzing galactose transfer from UDP-galactose to Gal-beta-1,4-Glc-ceramide 1. The enzyme can also catalyze subsequent additions of galactose to iGb3 itself to form polygalactose structures. A3GALT2 belongs to the GT6 glycosyltransferase gene family alongside ABO and GGTA1, with substrate specificity determined by amino acid residues at the binding pocket 1. In xenotransplantation research, A3GALT2 has emerged as a relevant target for genetic modification alongside GGTA1 and CMAH to reduce xenogeneic rejection 2. However, studies demonstrate that silencing A3GALT2 in GGTA1-knockout pigs does not significantly reduce alpha-gal epitope levels or antibody-mediated rejection in pig-to-human/primate xenotransplantation models 3. Triple knockout of GGTA1/CMAH/A3GALT2 pigs showed variable effects on human antibody binding depending on cell type, suggesting organ-specific considerations for xenograft engineering 4. In humans, A3GALT2 loss-of-function mutations are associated with markedly reduced plasma insulin C-peptide concentrations 5. A3GALT2 deficiency does not impact invariant natural killer T cell development or function 6, suggesting iGb3 is not critical for iNKT selection.