In this study, conditional knockout of SENP2 in the developing placenta results in trophoblast defects that are similar to those seen in a global knockout of SENP2. In both cases there is resultant CHD with hypoplastic chambers, thinning myocardium, and an absence of atrioventricular endocardial (AV) cushions. Here, SENP2 is linked to coronary artery disorder.