Genome-wide CRISPR-Cas9 knock out screens in MM have recently highlighted the role of CRL4CRBN E3 ligase associated proteins, including COP9 signalosome (CSN) members and certain E2 ubiquitin-conjugating enzymes, in mediating IMiD sensitivity and resistance through their regulation of CRBN-mediated substrate degradation (68, 69). Here, CRBN is linked to Miyoshi myopathy.