CRPPA (CDP-L-ribitol pyrophosphorylase A) is a cytidylyltransferase enzyme essential for protein O-linked mannosylation, specifically catalyzing the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate 1. This CDP-ribitol product serves as a critical substrate for the biosynthesis of phosphorylated O-mannosyl trisaccharides on alpha-dystroglycan, which are required for high-affinity binding to laminin G-like domain-containing extracellular proteins 1. The enzyme also shows activity toward other pentose phosphate sugars, mediating formation of CDP-ribulose or CDP-ribose 1. CRPPA mutations cause severe dystroglycanopathies, including Walker-Warburg syndrome and limb-girdle muscular dystrophy, characterized by congenital muscular dystrophy with brain and eye anomalies 23. These conditions result from defective alpha-dystroglycan glycosylation, leading to impaired sarcolemma stability and neuronal migration 4. Clinically, CDP-ribitol concentrations are reduced in patients with CRPPA mutations and can serve as a diagnostic biomarker 1. Importantly, dietary supplementation with ribitol or ribose can restore CDP-ribitol levels and correct the O-glycosylation defect in a mutation-dependent manner, offering potential therapeutic approaches 1.