DPM3 is a regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex located on the endoplasmic reticulum membrane 1. DPM3 stabilizes the catalytic DPM1 subunit through its C-terminal coiled-coil domain, tethering DPM1 to the ER membrane and preventing its proteasomal degradation 2. This tripartite complex (DPM1, DPM2, DPM3) generates mannosyl donors essential for N-glycosylation, O-mannosylation, and glycosylphosphatidylinositol anchor synthesis 1. Biallelic DPM3 mutations cause muscular dystrophy-dystroglycanopathy, characterized by deficient alpha-dystroglycan glycosylation and muscle weakness 3. Clinical presentations include limb-girdle muscular dystrophy with disease onset ranging from childhood to adulthood, dilated cardiomyopathy, and abnormal N-glycosylation profiles consistent with congenital disorder of glycosylation type 1 4. Recent evidence indicates DPM3 defects can also present with neuromuscular involvement, global developmental delay, intellectual disability, seizures, white matter abnormalities, and variable cardiomyopathy 5. Reduced O-mannosylation of alpha-dystroglycan and aberrant N-glycosylation of beta-dystroglycan in skeletal muscle characterize DPM3 pathology 6.