nephrocystins

Nephrocystins are a group of proteins that play a critical role in the development and maintenance of the kidney, particularly in the formation and function of renal cysts. These proteins are associated with autosomal recessive polycystic kidney disease (ARPKD), a genetic disorder characterized by the abnormal growth of cysts in the kidneys, leading to impaired renal function and potential end-stage kidney disease.

The nephrocystins include at least three main proteins: PKHD1 (fibrocystin/polyductin), NPHP1 (nephrocystin-1), and NPHP3 (nephrocystin-3). These proteins are part of a broader family of proteins involved in primary cilia function, which are hair-like structures found on the surface of many cells. Primary cilia act as cellular antennae, sensing environmental cues and transmitting signals that regulate cell division, movement, and differentiation.

PKHD1, encoded by the *PKHD1* gene, is the most extensively studied nephrocystin. It is localized to the primary cilium and basal bodies of epithelial cells in the kidney, liver, and pancreas. Mutations in *PKHD1* disrupt its function, leading to abnormal cyst formation in the kidneys and other organs. NPHP1 and NPHP3, encoded by *NPHP1* and *NPHP3* respectively, also localize to primary cilia and interact with PKHD1. Mutations in these genes are linked to various forms of nephronophthisis, a progressive kidney disease that often leads to cystic changes and eventual kidney failure.

The precise mechanisms by which nephrocystins regulate cyst formation remain under investigation, but they are thought to influence cellular signaling pathways, such as those involving calcium, planar cell polarity, and Wnt/β-catenin. Dysregulation of these pathways contributes to the abnormal proliferation and fluid accumulation in cysts, exacerbating kidney disease progression. Research into nephrocystins continues to offer insights into the molecular basis of cystic kidney diseases and potential therapeutic targets for treatment.