In summary, we uncovered for the first time that Grpel2 markedly attenuated heart dysfunction and cardiac remodeling in DCM by suppressing mitochondrial dysfunction, oxidative stress and aopotosis through Nr2f6 mediation the import of DLST into mitochondria in cardiomyocytes (Fig. 8). Here, GRPEL2 is linked to familial dilated cardiomyopathy.