Enhanced desumoylation in murine hearts by overexpressed SENP2 leads to congenital heart defects and cardiac dysfunction

► We studied the effect of de-sumoylation on heart development in a transgenic model. ► Increased desumoylation by overexpressed SENP2 in heart caused cardiac defects and dysfunction. ► SENP2 overexpression also caused defect in cardiomyocyte proliferation. ► SUMO-1 overexpression rescued cardiac structural phenotypes in SENP2-Tg mice. ► Balanced SUMO conjugation is essential for normal heart development and function.