Despite the severe pulmonary toxicity noted with VLX1570 in the present study, efforts directed at identifying DUB inhibitors with greater therapeutic indices appear warranted based on the unique mechanism of action, robustness of preclinical antitumor activity, and activity of the DUB inhibitors in MM resistant to PIs targeting the 20S proteasome subunit. Here, ZUP1 is linked to Miyoshi myopathy.