[
Nature,
1999]
Advances in human genetics have meant that the genes mutated in human diseases can be identified exclusively by their location in the genome. But how do we work out the cellular functions of the associated protein products? Reports on pages 383 and 386 of this issue begin to address this problem for two proteins - polycystin-1 (PKD1) and polycystin-2 (PKD2) - that are defective in human kidney disease. From their studies of the nematode worm Caenorhabditis elegans, Barr and Sternberg present evidence that homologues of the polycystins act together in a signal-transduction pathway in sensory neurons. Chen et al., by contrast, have used an oocyte-expression system in the from Xenopus laevis to show that a homologue of PKD2 is associated with the activity of a cation channel. These results support the hypothesis that polycystin-related proteins belong to a hitherto unknown class of signal-transduction molecules.