As mentioned above, it would be exciting to investigate if the expressions of ADAM10, ADAM17, MMP2, and other MMPs are altered in endothelial cells in pathological conditions, such as cardiac surgery and cavernous cerebral malformations, thereby influencing Robo4 shedding to affect Robo4 signaling, attributing to the related pathogenesis. Here, ROBO4 is linked to famililal cerebral cavernous malformations.