RASA1 encodes a GTPase-activating protein (GAP) that functions as a critical negative regulator of Ras signaling by facilitating the transition of Ras proteins from their active GTP-bound state to inactive GDP-bound state 1. The protein plays essential roles in vascular development, particularly in angiogenesis and lymphatic vessel formation. RASA1 physically interacts with EPHB4 to regulate lymphatic valve development by dampening Ras-MAPK activation induced through the PIEZO1 oscillatory shear stress sensor 2. This EPHB4-RASA1 signaling axis is crucial for proper cerebrovascular development and arteriovenous network formation 3. Loss-of-function mutations in RASA1 cause capillary malformation-arteriovenous malformation syndrome (CM-AVM), characterized by multifocal capillary malformations, arteriovenous malformations, and various lymphatic anomalies including pleural effusions, lymphatic malformations, and central conducting lymphatic anomalies 14. RASA1 mutations are also found in certain cancers, including lung adenocarcinomas and squamous cell carcinomas, where they contribute to tumor development through dysregulated Ras-MAPK signaling 56. The protein's dysfunction leads to abnormal angiogenic remodeling that cannot be compensated by other RasGAPs, highlighting its unique role in vascular biology 1.