ALG5 encodes dolichyl-phosphate beta-glucosyltransferase, a key enzyme in the N-glycosylation pathway 1. Operating on the cytoplasmic side of the endoplasmic reticulum membrane, ALG5 catalyzes glucose addition to dolichol-linked oligosaccharide precursors, producing dolichyl-beta-D-glucosyl phosphate as a substrate for downstream glycosyltransferases (ALG6, ALG8, ALG10) 1. This process is essential for synthesizing the 14-sugar Glc(3)Man(9)GlcNAc(2)-PP-Dol structure ultimately transferred to nascent proteins by oligosaccharyltransferases. Clinically, monoallelic ALG5 variants cause atypical polycystic kidney disease with small renal cysts, interstitial fibrosis, and progressive renal failure (reaching end-stage disease between 62-91 years) 2. ALG5 haploinsufficiency impairs polycystin-1 maturation and membrane localization, demonstrating how reduced ALG5 activity compromises protein N-glycosylation in renal epithelial cells 2. In bone metabolism, ALG5 downregulation associates with osteoporosis by impairing osteogenic differentiation through reduced N-glycosylation of SLC6A9, which decreases glycine uptake in mesenchymal stem cells 3. Additionally, ALG5 and STT3A upregulation in aged hippocampus sustains glucose homeostasis and cognitive function through N-glycosylation-dependent metabolic adaptation 4. ALG5 also functions as a host factor required for transmissible gastroenteritis virus infection through N-glycosylation of aminopeptidase N 5.