p120RasGAP was the first GAP to be identified [24, 32–34], is a major downregulator of RAS signaling [35–39], and is extensively mutated in the RASopathy, capillary malformation-arteriovenous malformation (CM-AVM) [40–43], however, the structural basis of its signaling is not well understood. Here, RASA1 is linked to RASopathy.