We demonstrate direct interaction of the TRPV4 ARD with inactive, GDP-bound RhoA, and further show how mutual TRPV4–RhoA inhibition and TRPV4 calcium-dependent activation of RhoA play important roles in modulating cellular outgrowth, both in cultured cells and in a fly model of TRPV4 neuropathy. This evidence concerns the gene TRPV4 and neuropathy.