RHOU is an atypical RHO GTPase with a high intrinsic guanine nucleotide exchange activity. Guanine nucleotide exchange factors (GEFs) are not needed for RHOU activation (Shutes et al. 2004, Saras et al. 2004). While some GTPase activator proteins (GAPs) have been reported to interact with RHOU (Bagci et al. 2020), they have not been shown to act on RHOU. Instead, GAPs may serve as RHOU effectors that enable its cross talk with other RHO GTPases (reviewed in Hodge and Ridley 2020). RHOU was shown to possess GTPase activity (Shutes et al. 2004), but the functional importance of GTP hydrolysis in the context of high intrinsic GEF activity and no known GAPs has not been elucidated.