4-Hydroxynonenal (4-HNE) is a major byproduct of lipid peroxidation, a process exacerbated by mitochondrial dysfunction and oxidative stress. Accumulation of 4-HNE protein adducts has been reported in several cardiovascular diseases, such as myocardial infarction, hypertension and heart failure in both rodents and humans. Therefore, identifying critical 4-HNE targets relevant to cardiac pathophysiology could help develop better therapies to treat heart failure.