Mutations or decreased expression of RNA-binding proteins (mRBPs) can lead to cardiomyopathies in humans. Here we defined RBPs in healthy and diseased primary cardiomyocytes at a system-wide level by RNA Interactome Capture. This identified 67 novel cardiomyocyte specific RBPs including several contractile proteins. Furthermore, we evaluated dynamic binding capacities of RBPs during pathologyical cardiac hypertrophy and identified Cytoplasmic polyadenylation element binding protein 4 (Cpeb4) as a dynamic RBP, regulating cardiac growth both in vitro and in vivo.