MM cells also exhibit baseline NRF1 activation and strongly depend on DDI2 for survival, and DDI2 knockout is cytotoxic to MM cells both in vitro and in vivo [Recent studies have shown that DDI2 knockout prevents proteolytic processing and nuclear translocation of NRF1, causing impaired proteasome activity recovery upon irreversible proteasome inhibition and thereby increasing sensitivity to PIs. Here, DDI2 is linked to Miyoshi myopathy.