We conclude that Lmod2 dictates in vivo cardiac function by its contribution to sarcomeric integrity and actin-myosin interactions via regulation of thin filament length, and that the Lmod2-TG model serves as the model where we can learn how repeated cellular-level insults (functional performance of elongated thin filaments at each contraction-relaxation cycle) progress into heart failure. This evidence concerns the gene MYH14 and heart failure.