Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure.

•The pathogenesis of human heart failure is complex, and the creation of new therapeutic strategies for human heart failure is critical.•Identifying the molecular pathways underlying heart failure is important to define potential new therapeutic targets.•Ankyrin polypeptides serve to target and stabilize membrane proteins in cardiomyocytes.•Ankyrin-G levels are altered in humans and mice with heart failure, and mice lacking ankyrin-G in cardiomyocytes develop cardiomyopathy and systolic dysfunction.•Mechanistically, ankyrin-G is necessary for the expression and localization of critical myocyte proteins essential for regulating cardiac structural and electrical activity.