PROJECT SUMMARY The RAS/extracellular signal regulated kinase (ERK) pathway is essential for proliferation, differentiation and cell survival. While somatic mutations on this signaling pathway cause one third of human malignancies, germline mutations in genes affecting RAS/ERK signaling cause a group of developmental disorders termed RASopathies with overlapping phenotypic features of varying severity. While individually rare, collectively, RASopathies comprise one of the largest groups of congenital disorders worldwide affecting ~1:1000-1:2500 individuals. Hence, the public health impact associated with altered RAS/ERK signaling due to somatic and germline pathogenic variants is enormous. RASopathies include neurofibromatosis type 1 (NF1), Noonan and Noonan-like syndromes (NS, NSML, NS-LAH), Costello (CS) and cardio-facio-cutaneous (CFC) syndromes, among others. 2021 marks the 20th anniversary of the discovery of the first human RASopathy gene providing a timely backdrop to convene the 7th International RASopathies Symposium: Pathways to a Cure - Expanding Knowledge, Enhancing Research, and Therapeutic Discovery to be held in Denver, Colorado, July 23-25th, 2021. The proposed symposium will continue to build on previous programs gathering clinicians, researchers, trainees, NIH and pharma representatives, and individuals and families affected by a RASopathy. The 2.5-day program integrates family participation in a poster session, advocate keynote talk, and panel discussions, as well as hosting deep science sessions for experts to share new research findings, data analyses, and case studies across the spectrum of RASopathies. The last session will address the significant topic of therapeutic approaches, whereby stakeholders and families can learn from each other what possibilities are in development and what outcomes are most needed. The conference chairs are Maria Kontaridis, PhD, Executive Director/Director of Research at the Masonic Medical Research Institute, Utica, NY and Amy Roberts, MD, Associate Professor of Medicine at Harvard Medical School and Director of Clinical Cardiovascular Genetics at Boston Children's Hospital. Two additional co-chairs, Marco Tartaglia, PhD, Director of the Genetics and Rare Diseases Research Division, OPBG, Rome, Italy, and Martin Zenker, MD, Director of the Institute for Human Genetics at Magdeburg University Germany, are included for their input after the 2020 European meeting on RASopathy disorders was cancelled amid the pandemic. Lisa Schoyer, PI and President of RASopathiesNet, together with co-investigators Lisa Schill, RASNet Vice President, and Beth Stronach PhD, Board Secretary, will include patient advocates in planning and implementation and will manage the logistics of the symposium.