R232, a reported TRPV4-neuropathy mutation site, does not directly participate in the interfacial contact but does form an intra-subunit salt-bridge with another disease-causing residue E183, which is likely important for tuning electrostatics and the local conformation of the RhoA-binding surface of the ARD (Supplementary Fig. 7e). This evidence concerns the gene TRPV4 and neuropathy.