Beta-1,4-N-acetyl-galactosaminyltransferase 2 (GALGT2) (GALGT2)

Beta-1,4-N-acetyl-galactosaminyltransferase 2 (GALGT2) is a glycosyltransferase enzyme that catalyzes the synthesis of the Sda blood group antigen on various glycoproteins and glycolipids [1]. In skeletal muscle, GALGT2 is naturally restricted to the neuromuscular junction, where it glycosylates alpha-dystroglycan and other membrane proteins [2]. Therapeutic overexpression of GALGT2 is being investigated as a surrogate gene therapy for Duchenne Muscular Dystrophy (DMD) and other muscular dystrophies [3]. By glycosylating substrates across the entire muscle fiber membrane (sarcolemma), GALGT2 promotes the recruitment of compensatory proteins such as utrophin, plectin, and laminin alpha-2 [2, 3]. This process stabilizes the muscle membrane and protects it from contraction-induced injury, effectively bypassing the functional requirement for dystrophin [3]. Clinical development focuses on using adeno-associated virus (AAV) vectors, such as rAAVrh74.MCK.GALGT2, to deliver the gene to muscle tissues to increase these protective glycosylation patterns [4].

Other names

B4GALNT2Sda synthaseCT GalNAc transferaseGalNAc-TUDP-GalNAc:Neu5Ac-alpha-2,3-Gal-beta-1,4-GlcNAc-R beta-1,4-N-acetylgalactosaminyltransferase 2

Overexpression of GALGT2 leads to the glycosylation of alpha-dystroglycan with the Sda carbohydrate antigen, which recruits compensatory proteins like utrophin and plectin to the sarcolemma to stabilize the muscle membrane [2, 3].