RHOBTB3 is a member of the Ras-like superfamily of proteins that is phylogenetically distinct from other related Ras-like families, which include, besides RHOBTB3, Rho, Miro, Ras, Ran, Arf and Rab (Boureux et al. 2007). Due to its similarity with RHOBTB1 and RHOBTB2 Rho GTPases, RHOBTB3 is sometimes classified as an atypical member of the RHO GTPase family. However, the GTPase domain of RHOBTB3 is divergent from other Ras-like superfamily members and actually displays ATPase activity (Espinosa et al. 2009). All three RHOBTBs 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).