In line with the notion that increased proton leak is maladaptive for the heart, our study shows that MTFP1 loss in cardiomyocytes reduces the mitochondrial membrane potential as a result of increased proton leak through the IMM (Fig. 2d, e, Fig. S2e–h) preceding the onset of cardiomyopathy. This evidence concerns the gene MTFP1 and cardiomyopathy.