Skeletal muscle atrophy is a common comorbidity of cancer. The cellular signaling mechanisms that regulate muscle size constitute a balance of the protein breakdown pathways upregulated during atrophy, and the protein synthesis pathways that are activated during skeletal muscle hypertrophy. In this issue of Cancer Cell, Acharyya et al. demonstrate a new and surprising regulatory axis that is centered around dystrophin, the protein that is mutated in settings of muscular dystrophy. These data reposition dystrophin as a signaling protein and connect an important cellular complex required for the structural integrity of muscle to the pathways that modulate muscle size.