ERK2 is required for SCFFBXL19-mediated RhoA ubiquitination [16], while Cerebral Cavernous Malformation 2 (CCM2) has been demonstrated to act as an important scaffolding protein in facilitating Smurf1-mediated RhoA degradation [18,19]. Here, RHOA is linked to famililal cerebral cavernous malformations.