RHOA and neuropathy: In addition, we introduced the R316A mutation that resulted in increased baseline calcium uptake, consistent with previous studies of neuropathy-causing mutations at the TRPV4-RhoA interface13, and dramatically weakened activation by 4α-PDD (Supplementary Fig. 1f–h), providing verification of our structure and strongly supporting the inhibitory role of RhoA in hTRPV4 function.