An understanding of the role of TRPV4 in mammalian kidney physiology begins in the nematode C. elegans. Worms are repelled by steep osmotic gradients, an adaptive mechanism presumably conserved to minimize the risk of acute changes in cell volume. Worms with mutated copies of a particular gene, while remaining fully motile, are oblivious to potentially harmful osmotic gradients; this gene was dubbed
osm-9 [1,2]. The OSM-9 protein bore a striking similarity to the transient receptor potential channel implicated in visual signal transduction in Drosophila [3]-the prototypical member of the now well-recognized TRP superfamily [4]. Several years later, the mammalian orthologue of OSM-9 was identified via homology screening [5,6] and other approaches [7,8]; it eventually became known as TRPV4 [9].