Importantly, we found that GRP75 promotes proto-Dbl degradation via the CHIP-mediated ubiquitin–proteasome pathway (UPP), and GRP75 expression modulates onco-Dbl-triggered Rho GTPases activation, which causes the striking derailment of endocytosis pathways inside ovarian cancer cells. The gene discussed is HSPA9; the disease is ovarian cancer.