RNF213 and endothelial dysfunction: Induced pluripotent stem cell–derived vascular endothelial cells from patients with Moyamoya disease with the RNF213 variant show decreased angiogenic activities,37,38 which could be attributed to endothelial dysfunction in cardiovascular systems.13 This observation aligns with the potential contribution of the mechanisms of VSA, with vascular smooth muscle hyperreactivity seen as the primary mechanism.39,40 Another study41 has shown that RNF213 attenuates WNT/calcineurin/NFAT signaling.