RHOBTB3 is an atypical member of the RHO GTPase family with a very divergent GTPase domain that actually displays ATPase activity (Espinosa et al. 2009). RHOBTB family proteins, in contrast to other RHO GTPases, possess other conserved domains in addition to the GTPase domain. The GTPase domain at the N terminus is followed by a proline rich region, a tandem of two BTB (broad complex, tramtrack, bric à brac) domains, and a conserved C terminal BACK (BTB and C terminal Kelch). Unlike RHOBTB1 and RHOBTB2, RHOBTB3 has a CAAX box (prenylation motif) domain (Berthold et al. 2008, Ji and Rivero 2016). RHOBTB proteins can form homo and heterodimers, but the role of dimerization in RHOBTB function is not known (Berthold et al. 2008, Ji and Rivero 2016). RHOBTB3 is ubiquitously expressed, with high levels in placenta, testis, pancreas, adrenal and salivary glands and neural and cardiac tissues (Berthold et al. 2016). RHOBTB3 is involved in CUL3 dependent protein ubiquitination (Berthold et al. 2008; Ji and Rivero 2016). RHOBTB3 is involved in retrograde transport from endosomes to the Golgi apparatus (Espinosa et al. 2009). RHOBTB3 participates in regulation of the cell cycle and in modulating the adaptive response to hypoxia (Ji and Rivero 2016). RHOBTB3 level is decreased in many tumor types and it is proposed to act as a tumor suppressor, although no pathogenic mutations have been reported (Berthold et al. 2008; Ji and Rivero 2016).