**7. Conclusions**

Cardiomyopathy is a significant clinical feature of DMD, with nearly all patients exhibiting cardiac dysfunction by their teens [13]. Improved clinical management of musculoskeletal and respiratory issues in DMD patients has uncovered cardiomyopathy as a significant contributor to morbidity and mortality [13]. The underlying pathology is complex, owing to the multiple functions of dystrophin in the cardiac myocyte, but calcium overload and mishandling due to membrane instability is a key mechanistic contributor to disease onset and progression. Currently utilized clinical therapies for DMD cardiomyopathy do not specifically target calcium handling defects and come with significant side effects. Gene therapeutic strategies to correct calcium handling defects show some promise in experimental models of DCM, but more work must be done to understand the potential benefits and risks of these strategies in models specific to DMD-related cardiomyopathy. Of note, increasing calcium cycling in the context of the membrane instability characteristic of DMD may exacerbate disease progression [19]. Continued work to understand the mechanistic underpinnings of DMD cardiomyopathy, specifically related to calcium handling, will enable a more targeted approach to therapeutic development for this disease.

**Author Contributions:** Conceptualization: M.L.L. and J.M.M.; literature review and original draft preparation: M.L.L., H.C., A.A.M., A.B.B.A.; revisions and editing: M.L.L., H.C., A.A.M., A.B.B.A., J.M.M.; figure and table preparation: M.L.L., H.C., A.A.M., A.B.B.A.; final manuscript approval: M.L.L., H.C., A.A.M., A.B.B.A., J.M.M.; acquisition of funding: J.M.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was funded by National Institutes of Health (AR071349, HL138490, HL122323, HL132874) and Muscular Dystrophy Association (513474).

**Conflicts of Interest:** The authors do not declare any conflict of interest.
