Mechanistically, this study identified that IMD alleviates DCM by up-regulating CPT-1β via CRLR/RAMP receptor complexes and phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt) signaling, suggesting that targeting IMD is a potential therapeutic strategy for DCM. Here, CALCRL is linked to familial dilated cardiomyopathy.