Gene therapy is considered a potential treatment for Duchenne muscular dystrophy (DMD). Researchers have been working on this for many years to find effective therapeutic targets. Here, we found that MRTF-A (myocardin-related transcription factor A) could activate the transcription of L-type Ca2+-channel-related protein CACNA1S (calcium voltage-gated channel subunit alpha1 S) by binding to the CarG box in the promoter of CACNA1S. However, increased phosphorylation and decreased expression of MRTF-A were observed, along with the expression of CACNA1S reduced in mdx mice. Further, the decreased expression and increased phosphorylation of MRTF-A could inhibit the release of Ca2+ via CACNA1S. Therefore, MRTF-A may be a potential molecular target for the diagnosis and treatment of DMD.