Summary Stanford University and the SLAC National Accelerator Laboratory propose to continue the Stanford-SLAC CryoEM Center (S2C2) as a National Center for Cryogenic Electron Microscopy to meet the growing demand for atomic-resolution structural biology. S2C2 will 1) upgrade and maintain six cutting-edge cryo-electron microscopes, 2) record and archive image data with comprehensive metadata, 3) assist users to overcome technical challenges in preparing vitrified samples suitable for high-resolution cryoEM structure determination and in data acquisition, 4) provide real-time data quality assessment, 5) ensure public accessibility of our resources regardless of user’s geographical location, 6) select user proposals based on scientific impact and readiness as judged by external experts’ evaluations, 7) disseminate cryoEM best practices through seminars, workshops, and user meetings, 8) train independent cryoEM researchers, 9) integrate and evaluate user feedback for facility improvement, 10) implement and validate new instrument and technology as developed , and 11) optimize center operational efficiency. Led by Dr. Wah Chiu, Dr. Michael Schmid and Dr. Britt Hedman, supported by an Advisory Committee comprising external expert scientists and user representatives, and leveraging SLAC's many decades of expertise in serving a wide range of scientific users, including those from IDeA states and under-resourced institutions, S2C2 will foster high-throughput cryoEM data generation, optimization of vitrified sample preparation, and cross-disciplinary training for novice and advanced users. Our collective efforts will shape the future of cryoEM structural biology, enabling unprecedented discoveries crucial to fundamental biomedical sciences.