ALG10B is an alpha-1,2-glucosyltransferase that catalyzes the final step of dolichol-linked oligosaccharide biosynthesis in the endoplasmic reticulum lumen, adding the third glucose residue to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol, a critical glycan precursor for protein N-linked glycosylation 1. This enzyme functions as an essential regulator of proper protein folding and trafficking, particularly for membrane proteins like HERG (Kv11.1) potassium channels 2. Clinically, ALG10B mutations cause multiple phenotypes reflecting N-glycosylation pathway disruption. A homozygous dual variant in ALG10/ALG10B produces congenital disorder of glycosylation-like features including epilepsy, brain atrophy, and sleep abnormalities 1. ALG10B missense mutations (p.G6S) cause long-QT syndrome by impairing HERG trafficking and channel function, resulting in prolonged cardiac action potentials and arrhythmia risk 2. Additionally, ALG10B mutations cause nonsyndromic hearing impairment through outer hair cell defects, indicating auditory system sensitivity to N-glycosylation perturbations 3. Genome-wide association studies link ALG10B variants to sleep duration, timing, and cardiac traits 1, suggesting broader roles in circadian regulation through GPR176 N-glycosylation 4. The glucosyltransferase activity protects HERG from drug-induced inhibition, explaining variable susceptibility to acquired long-QT syndrome 5.