RHOBTB2, like other RHOBTB family members, RHOBTB1 and RHOBTB3, binds CUL3 (cullin-3) (Berthold et al. 2008), a core component of BTB-CUL3-RBX1 E3 ubiquitin ligase complexes. Binding of GTP to RHOBTB2, facilitated by the HSP90 chaperone complex, enables binding of RHOBTB2 to CUL3 (Manjarrez et al. 2014). RHOBTB2 is thought to act as the regulatory BTB component of the BTB-CUL3-RBX1 complex by recruiting target proteins for ubiquitination and subsequent proteasome-mediated degradation (Wilkins et al. 2004). RHOBTB2 is a substrate adaptor for Musashi 2 (MSI2), targeting it to CUL3 complexes for ubiquitination and proteasomal degradation, thus suppressing tumorigenesis (Choi et al. 2017).