To unravel the molecular mechanisms underpinning early OXPHOS dysfunction in the CS mouse model we performed a label-free proteomic analysis (Figure 3A) of (a) 4 CS mouse tissues (skeletal muscle, heart, liver, and brain) obtained at 3 and 12 weeks of age from homo- and heterozygous HRAS p.G12S animals, (b) human primary skin fibroblasts obtained from 3 patients with CS carrying HRAS p.G12S or HRAS p.G12A mutations, and (c) human primary skin fibroblasts expressing ectopic HRAS p.G12S or HRAS p.G12A lentiviral constructs (n = 4 clones for each construct). The gene discussed is HRAS; the disease is Cowden syndrome 1.