This study demonstrates that the splicing regulator SLM2 is up-regulated in the failing myocardium of DCM patients and is actively involved in cardiac mRNA splicing of multiple pivotal cardiac genes including TTN. Importantly, loss  or overexpression of SLM2 results in hallmarks of heart failure and pinpoints to its functional role in the heart. This evidence concerns the gene TTN and familial dilated cardiomyopathy.