Autosomal dominant polycystic kidney disease (ADPKD) affects millions of individuals worldwide, is one of the most common, potentially lethal single-gene disorders, is the fourth leading cause of kidney failure in the United States, and annually costs over one billion dollars to treat. ADPKD research is now seeing an intense effort to define the functions of polycystin-1 and-2, the proteins encoded by the PKD1 and PKD2 genes, and there is now a clear target in sight. In this issue of PNAS, a report by Gonzalez-Perrett et al.(1) presents evidence that polycystin-2, the protein product of the PKD2 gene, functions as a nonspecific Ca2+-permeable cation channel. In this respect, PKD research appears to be taking a page from the notebook on cystic fibrosis, an inherited disease in which pulmonary and pancreatic epithelial dysfunction is attributed to a defect in transepithelial ClJ transport (2).

Polycystic kidneys have a striking appearance (Fig. 1). Typically, both kidneys are massively enlarged as a consequence of the growth of hundreds or thousands of cysts scattered throughout the renal cortex and medulla. The gross anatomical distortion caused by these cysts is thought to be responsible for the progressive loss of kidney function associated with this disease and the renal failure experienced by approximately 50% of affected individuals.