HRAS and Cowden syndrome 1: Here, we performed a comprehensive analysis of the molecular determinants of CS using untargeted proteomics, bioenergetics, and molecular biology methods on a collection of biological models: tissues of a HRAS p.G12S CS mouse model, skin fibroblasts from patients with CS, CS hiPSC-CMs, human skin fibroblasts transduced with mutant forms of HRAS p.G12S and HRAS p.G12A, and a HRAS p.G12V zebrafish model of CS.