PRKCSH encodes the regulatory β-subunit of glucosidase II, an endoplasmic reticulum (ER) protein essential for N-glycan processing of immature glycoproteins 1. It sequentially cleaves the two innermost α-1,3-linked glucose residues from the Glc₂Man₉GlcNAc₂ oligosaccharide precursor during protein maturation. PRKCSH is required for efficient biogenesis and trafficking of polycystin-1 (PKD1) to the primary cilia 1, a central determinant of cyst pathogenesis in polycystic diseases. Germline PRKCSH mutations cause autosomal dominant polycystic liver disease (ADPLD), characterized by severe hepatic cysts with minimal kidney involvement 2. Loss-of-function mutations in PRKCSH result in defective polycystin-1 maturation and trafficking, triggering cyst formation through reduced functional polycystin dosage 3. PRKCSH is one of the two major genes for ADPLD, alongside SEC63 4, accounting for a significant proportion of genetically defined cases. Among patients with ADPLD without PRKCSH or SEC63 mutations, variants in PRKCSH can still be identified as alternative genetic causes 5. Beyond inherited polycystic disease, PRKCSH is upregulated in colorectal cancer and modulates radioresistance through ER stress pathways, suggesting broader roles in cancer biology 6. Genetic testing for PRKCSH variants is clinically valuable for diagnosis and disease classification in polycystic kidney and liver disease patients.