Taken together, our mouse model provides insights into the pathological mechanisms of cardiomyopathy in the presence of a non-sarcomeric HCM-causing mutation in CSRP3. Furthermore, our work indicates that proteasomal degradation by the UPS is responsible for the depletion of HCM-associated mutant MLP, which is the underlying driver of the disease. This evidence concerns the gene CSRP3 and cardiomyopathy.