Rare inherited diseases provide a unique window into specific aspects of physiology. In turn, our knowledge of physiology can help understand the molecular basis of these disease, enable precise diagnosis and provide a platform for the development of improved treatments.At Great Ormond Street, we have a specialized renal tubular clinic caring for more than 200 patients with mostly Mendelian disorders of tubular function.I will use EAST syndrome as an example of successful collaboration between clinic and physiology that led to the first recognition of this disorder, the identification of the molecular basis and novel observations of the specific clinical consequences. These investigations now allow us to provide affected patients and their families a specific diagnosis, as well as clinical and genetic counseling. Moreover, we have been able to establish animal models of the disease, enabling the testing of potential treatments.