The ubiquitin‐proteasome pathway is involved in cell dedifferentiation, stress response, and cell cycle control.[37] Targeting the proteasome machinery with small molecules has been successfully translated into clinical cancer therapies.[38] In the current study, we also provide evidence for using a proteasome inhibitor bortezomib to overcome MCB1‐mediated resistance and restore the targeted drug response. This evidence concerns the gene PSMD4 and cancer.