PKHD1 encodes fibrocystin/polyductin, a large transmembrane protein essential for kidney and liver development. The protein promotes ciliogenesis in renal epithelial cells and regulates tubule formation and luminal architecture maintenance. PKHD1 functions in epithelial morphogenesis by controlling bipolar cell division through centrosome regulation and mitotic spindle assembly, while maintaining oriented cell division via the planar cell polarity pathway 1. It regulates cell-cell adhesion and participates in cholangiocyte proliferation, with potential involvement in collecting-duct and biliary differentiation. Biallelic PKHD1 mutations cause autosomal recessive polycystic kidney disease (ARPKD), characterized by fibrocystic kidney changes, congenital hepatic fibrosis, and variable clinical presentation 2. Disease severity correlates with mutation type and affected protein regions; biallelic null variants cause the most severe phenotypes, while missense variants produce milder presentations 1. The condition typically manifests in early childhood but can present in adulthood with hepatic predominance 3. ARPKD leads to progressive chr6 kidney failure (mean onset age 4 years) and portal hypertension in approximately 44% of patients 4. Organoid studies reveal that PKHD1 mutations increase TGFβ pathway activation in cholangiocytes, driving hepatic fibrosis through myofibroblast activation and collagen production 5. Molecular diagnosis through PKHD1 sequencing is crucial for clinical management and prognostic counseling.