fibrocystinpolyductin

Fibrocystin-polyductin, also known as fibrocystin or polyductin, is a large single-pass transmembrane protein encoded by the PKHD1 gene in humans. It is primarily expressed in the kidney and liver, particularly in the epithelial cells lining renal tubules and bile ducts, and localizes to primary cilia and the apical membranes of these cells.

The PKHD1 gene is located on chromosome 6p12 and produces several transcript variants through alternative splicing. The protein features a substantial extracellular N-terminal region, a single transmembrane helix, and a cytoplasmic C-terminal tail.

Fibrocystin-polyductin is believed to participate in tubular morphogenesis and maintenance of ductal architecture, possibly through ciliary signaling pathways that regulate cell proliferation, differentiation, and extracellular matrix interactions. The precise mechanisms remain under investigation.

Mutations in PKHD1 are the cause of autosomal recessive polycystic kidney disease (ARPKD), a ciliopathy characterized by massively enlarged, echogenic kidneys at birth or in infancy and by congenital hepatic fibrosis. The disease spectrum ranges from perinatal kidney failure to later cystic changes; hepatic involvement can lead to portal hypertension.

Diagnosis typically involves genetic testing for PKHD1 mutations and imaging findings. There is no cure; management is supportive and multidisciplinary, addressing kidney function, hypertension, and liver-related complications. Research continues to elucidate fibrocystin-polyductin’s exact functions and its role in ciliary signaling, with implications for targeted therapies.