DPAGT1 (dolichyl-phosphate N-acetylglucosaminephosphotransferase 1) catalyzes the initial and rate-limiting step of N-linked glycosylation by transferring N-acetylglucosamine-1-phosphate from UDP-GlcNAc onto dolichyl phosphate to form GlcNAc-P-P-dolichol at the endoplasmic reticulum membrane 1. This lipid-linked oligosaccharide intermediate is subsequently elaborated with nine mannoses and three glucoses before transfer to nascent proteins by oligosaccharyltransferases, enabling proper protein folding and function 2. DPAGT1 mutations cause two major human diseases: Congenital Disorder of Glycosylation type 1J (DPAGT1-CDG) and Congenital Myasthenic Syndrome 13 (CMS13) 3. DPAGT1-CDG presents with multisystem manifestations including failure to thrive, seizures, and psychomotor retardation, with severe cases resulting in intrauterine death 4. CMS13 manifests as neuromuscular junction dysfunction with limb-girdle weakness 5, affecting approximately 9.8% of genetically diagnosed CMS patients in Indian cohorts 5. Clinically, DPAGT1 inhibition suppresses HER2 shedding and trastuzumab resistance in breast cancer by preventing N-glycosylation of ADAM10 sheddase 1. Emerging therapeutic approaches targeting dopamine D2 signaling show promise for DPAGT1-CDG 6, while O-GlcNAcylation modulation may provide neuroprotection in glycosylation disorders 7.