Indeed, overactivation of CRLs has been characterized in tumor growth and progression and the enzymes implicated in the neddylation pathway (e.g., NAE1/UBA3, UBE2M/UBE2F, NEDD8 E3 ligases) are often overexpressed in different human cancers, including MM [59]. This evidence concerns the gene NEDD8 and Miyoshi myopathy.