Robo4 was further discovered to be a novel endothelial factor contributing to the etiology of bicuspid aortic valve, a common congenital heart defect, and a reduction in the expression of or structural disruption of Robo4 in EC lines resulted in a synthetic repertoire suggestive of the endothelial-to-mesenchymal transition [114]. This evidence concerns the gene ROBO4 and Bicuspid aortic valve.