Studies of TRPV4 disease mutants in heterologous systems have demonstrated that both neuropathy and skeletal dysplasia mutations lead to gain of ion channel function, increased basal and stimulated TRPV4-mediated calcium influx, and cytotoxicity that can be rescued with channel antagonists1,2,7,16,24,25. This evidence concerns the gene TRPV4 and skeletal dysplasia.