Duchenne muscular dystrophy (DMD), a progressive and debilitating muscle disorder, has proved intractable to therapy, but now an approach involving a molecule already in clinical trials for a different disorder, may provide a new treatment window. Following on the observation that inflammation plays a role in disease pathology, Gehrig et al. targeted inflammatory mediators phosphorylated JNK, phosphorylated I-kappa-B kinase complex and tumor necrosis factor-α by expressing heat shock protein 72 (Hsp72). Using several mouse models of DMD and different methods for elevating Hsp72, the authors were able to show improvement in muscle strength and reductions in the pathological changes characteristic of the disorder. However, when they measured levels of their original inflammatory signaling targets, the researchers found these molecules were unchanged in mice overexpresssing Hsp72. This led the group to a different target for Hsp72, the sarcoplasmic/endoplasmic reticulum Ca-ATPase (SERCA), which was already known to interact with Hsp72 during times of cellular stress, as well as to be compromised in DMD patients. The researchers found increased activity of the molecule in muscle homogenates of mice overexpressing Hsp72, whereas protein and RNA levels were unchanged, suggesting that the sparing effects of Hsp72 are a result of its ability to preserve the function of SERCA. Finally, a pharmacologic inducer of Hsp72, BGP-15, which is in trials for type 2 diabetes, increased SERCA activity in dystrophic mice and improved muscle function, suggesting an immediate path to the clinic for DMD patients. (Nature 484, 394–398, 2012)