GGTA1 encodes α1,3-galactosyltransferase, an enzyme that synthesizes the α-gal epitope on cell surface glycoproteins and glycolipids 1. In humans and Old World primates, GGTA1 is naturally inactivated by frameshift mutations, resulting in loss of α-gal epitope expression and production of naturally occurring anti-Gal antibodies that recognize this xenoantigen 1. The α-gal epitope is the primary carbohydrate barrier to pig-to-human xenotransplantation; human preformed antibodies targeting this antigen mediate hyperacute rejection 2. GGTA1 knockout in donor pigs, often combined with inactivation of CMAH and β4GalNT2 genes, substantially reduces human antibody binding to porcine cells and xenograft immunogenicity 23. Clinical xenotransplant studies using GGTA1-knockout pig kidneys demonstrate that genetic modification alone is insufficient to prevent rejection without comprehensive immunosuppression; acute antibody-mediated rejection still occurs despite GGTA1 elimination, driven by T cell responses and antibodies targeting non-α-gal epitopes 45. GGTA1 knockout pigs also exhibit reduced platelet consumption and lower anti-gal-mediated hemolysis, improving xenotransfusion viability 63. While GGTA1 inactivation represents a critical first step in xenotransplantation, addressing remaining immunological barriers requires additional genetic modifications and optimized immunosuppressive protocols.