ALG6 encodes an α-1,3-glucosyltransferase that catalyzes a critical step in N-linked protein glycosylation within the endoplasmic reticulum 1. Specifically, ALG6 adds the first glucose residue to the lipid-linked oligosaccharide intermediate Man9GlcNAc2-PP-Dol, producing Glc1Man9GlcNAc2-PP-Dol, which serves as substrate for the next biosynthetic enzyme ALG8 1. This glucose addition is essential for assembling the complete 14-sugar dolichol-linked oligosaccharide precursor that nascent proteins require for proper N-glycosylation 1. Mutations in ALG6 cause congenital disorder of glycosylation type Ic (CDG-Ic), now the second most common N-glycosylation disorder 2. ALG6-CDG presents with a recognizable phenotype dominated by neurological manifestations: hypotonia, developmental delay, and epilepsy present universally, while ataxia, proximal muscle weakness, and behavioral abnormalities (autistic features, depression) occur in most patients 2. Additional features include failure to thrive, coagulation anomalies, and in severe cases, protein-losing enteropathy leading to early mortality 2. The common mutations p.A333V and p.I299Del show variable phenotypic severity 2. Beyond glycosylation, ALG6 is required for host susceptibility to transmissible gastroenteritis virus infection, operating through N-glycosylation of aminopeptidase N 3. ALG6-CDG also associates with cardiomyopathy risk among carbohydrate metabolism disorders 4.