WWOX is a tumor suppressor that is commonly lost in several human malignancies. Several reports have implicated WWOX function in cellular metabolism. Abu-Remaileh et al. screened for the metabolic function of WWOX using engineered mouse models in which the murine Wwox gene was specifically deleted in the main metabolic peripheral organs including liver, adipose tissue, and skeletal muscle. They found that only mice with skeletal muscle-specific ablation of Wwox develop a phenotype resembling metabolic syndrome, as manifested by hyperglycemia, obesity, and dyslipidemia.