GANAB encodes the catalytic alpha subunit of glucosidase II, an endoplasmic reticulum (ER) enzyme that sequentially removes the two innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor during N-glycan processing of immature glycoproteins 1. This glucose trimming is essential for proper protein folding and quality control in the ER, where the balance between GANAB-mediated deglycosylation and UGGT-mediated reglycosylation determines protein maturation 2. GANAB is critical for maturation and cell surface/ciliary localization of polycystin-1 (PKD1) and polycystin-2 (PKD2), the primary determinants of cyst pathogenesis 3. Loss-of-function GANAB mutations impair polycystin trafficking through defective protein biogenesis, triggering unfolded protein response and cyst formation 32. Pathogenic GANAB variants cause autosomal dominant polycystic liver disease (ADPLD) with minimal kidney involvement, and can also present as autosomal dominant polycystic kidney disease (ADPKD) 45. Among genetically confirmed ADPKD cases, GANAB accounts for a minority of diagnoses, with loss-of-function variants significantly associated with disease 6. GANAB represents a minor but clinically important locus bridging kidney and liver cystic disease through ER protein biosynthetic pathway disruption 5.