KRIT1 and cerebral cavernous malformation: Taken together, our findings point to a novel mechanism whereby the downregulation of Notch signaling induced by KRIT1 loss-of-function can be a consequence of altered redox homeostasis and signaling and may in turn contribute to the upregulation of established markers of endothelial dysfunction (Figure 5), thus predisposing not only to the pathogenesis of CCM disease but also to the development of atherosclerosis and associated cardiovascular comorbidities.