Pkd2

PKD2 is the gene that encodes polycystin-2, a member of the transient receptor potential (TRP) channel family, also known as TRPP2. The protein functions as a nonselective cation channel that conducts calcium and other ions across cell membranes. In humans, PKD2 is located on chromosome 4 (4q21). The protein contains multiple transmembrane domains and localizes to the primary cilium and the plasma membrane of renal epithelial cells, where it participates in calcium signaling.

PKD2 operates in conjunction with polycystin-1 (PKD1) to form a receptor–ion channel complex that responds to mechanical cues such as fluid flow in kidney tubules. Through this complex, mechanical stimulation can trigger calcium influx, influencing processes involved in tubular development, cell proliferation, and differentiation. Disruption of PKD2 function can perturb calcium signaling and ciliary signaling pathways, contributing to abnormal renal tubular development and cyst formation.

Mutations in PKD2 cause autosomal dominant polycystic kidney disease type 2 (ADPKD2). Compared with PKD1-related disease, ADPKD2 often has a later onset and more variable progression, though clinical outcomes vary widely among individuals. Affected individuals typically develop bilateral renal cysts and may also have hepatic cysts; hypertension and progressive renal impairment can occur over time.

Genetics and inheritance are consistent with autosomal dominant transmission, with a 50% risk of passing a PKD2 mutation to offspring. Genetic testing can confirm diagnoses and guide family planning. Animal models, including Pkd2 knockout mice and zebrafish, have supported the role of polycystin-2 in renal ciliary function and calcium signaling, contributing to understanding of disease mechanisms and potential therapies.