In the current study, we aimed to test whether the adverse effects of restrictive cardiomyopathy (RCM OMIM 115210)-E143K ELC and dilated cardiomyopathy (DCM OMIM 606685)-D94A RLC mutations that exert severe myofilament impairments could be rescued by phosphomimetic S15D-RLC reconstituted in Tg-E143K versus Tg-WT ELC fibers and Tg-D94A versus Tg-WT RLC preparations. Here, TG is linked to restrictive cardiomyopathy.