Altogether, our study emphasizes the key role of RYR1-mediated intracellular Ca2+ mishandling in myogenic differentiation (and to some extent in the motor outcome) in DMD and the potential value of RYR stabilizers as adjunctive therapy in human dystrophinopathies. This evidence concerns the gene RYR1 and neuromuscular disease caused by qualitative or quantitative defects of dystrophin.