In signal transduction of metazoan cells, transient receptor potential (TRP) ion channels have been identified to respond to diverse external and internal stimuli, among them osmotic and mechanical stimuli. This chapter summarizes findings on the TRPV subfamily, both its vertebrate and invertebrate members, with a focus on TRPV4. Of the six mammalian TRPV channels, TRPV1, 2, and 4 were demonstrated to function in transduction of osmotic and mechanical stimuli. Invertebrate TRPV channels, five in C. elegans and two in Drosophila, have been shown to play a role in mechanosensation, such as hearing and proprioception in Drosophila and nose touch in C. elegans, and in the response to tonicity in C. elegans. TRPV4 has been found to function in cellular as well as systemic osmotic homeostasis in vertebrates. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue mechano- and osmosensory, not olfactory, deficits of the TRPV mutant line
osm-9 in C. elegans, despite not more than 25 percent orthology of the respective amino acid sequences.