These studies uncovered OTUD6B as a central dependency in MM, whose activity directly impinges on the RBP LIN28B in order to drive a MYC‐dependent cell cycle activatory program, that links post‐translational activity of the UPS with post‐transcriptional gene regulation and may contribute to both the conversion of MGUS to MM and the maintenance of MM. Here, OTUD6B is linked to Miyoshi myopathy.