ALG8 is an alpha-1,3-glucosyltransferase that catalyzes the addition of the second glucose residue during dolichol-linked oligosaccharide biosynthesis in the endoplasmic reticulum, producing Glc₂Man₉GlcNAc₂-PP-Dol as substrate for downstream enzymes 12. This enzymatic step is essential for N-linked protein glycosylation, a critical post-translational modification required for proper protein folding and trafficking. ALG8 is particularly important for polycystin-1 maturation and trafficking to the plasma membrane and primary cilia; loss-of-function mutations impair polycystin-1 biogenesis, disrupting the normal signaling cascade that prevents cyst formation 3. Pathogenic ALG8 variants cause two distinct disease phenotypes: congenital disorder of glycosylation 1H (ALG8-CDG), presenting with hypotonia, protein-losing enteropathy, hepatic involvement, intellectual disability, and multisystem complications 4; and autosomal dominant polycystic liver disease with variable kidney involvement 56. In polycystic disease cohorts, ALG8 variants occur in approximately 1.3% of families, typically causing mild-to-moderate kidney cysts and frequent liver cysts, with rare kidney failure 7. ALG8 represents an important minor locus in polycystic kidney disease genetics, requiring inclusion in comprehensive clinical genetic panels alongside major genes PKD1 and PKD2.