Robert Semple, Chair of Translational Molecular Medicine at the University of Edinburgh, is a world-leading clinical molecular endocrinologist and authority on human metabolic and growth disorders. He discovered that primary insulin resistance lacks fatty liver and dyslipidaemia, showing that common “IR syndrome” is an admixture of loss and gain of tissue insulin action, with important implications for reducing IR-related disease. He showed the potential of monoclonal antibodies to activate mutated insulin receptors, massively extending this in Edinburgh to 14,000 mutations to unblock a translational bottleneck. Semple discovered mosaic activating PIK3CA mutations in disfiguring, asymmetric overgrowth. He assembled the largest cohort of patients with this new disease, determined its natural history, proposed classification, developed consensus for care and showed effective treatment with sirolimus.