MPDU1 (mannose-P-dolichol utilization defect 1) is essential for utilizing mannose-P-dolichol (Dol-P-Man) in the biosynthesis of N-linked and O-linked oligosaccharides and GPI anchors 1. The protein facilitates the stepwise synthesis and transfer of lipid-linked oligosaccharides (LLOs) during N-glycosylation, a co-translational modification critical for proper protein folding, stability, and trafficking 2. MPDU1 is notably the first gene identified to affect donor substrate utilization rather than biosynthesis itself 3. Mutations in MPDU1 cause Congenital Disorder of Glycosylation type If (CDG-If), characterized by defective glycosylation leading to incomplete, poorly transferred precursor oligosaccharides lacking mannose and glucose residues 3. CDG-If presents with severe psychomotor retardation, seizures, failure to thrive, dry skin with erythroderma, impaired vision, and severe ichthyosis 34. The disorder exemplifies how defective LLO biosynthesis impairs glycosylation of multiple glycoconjugate types 3. Clinically, MPDU1-CDG warrants inclusion in workups for infantile ichthyosis and multisystem metabolic disorders 4. MPDU1 deficiency also affects cell adhesion molecules like CEACAM1, demonstrating broader functional consequences beyond glycosylation alone 2. As a CDG affecting carbohydrate metabolism, MPDU1 mutations carry potential for cardiac complications 5.