Primary focal hyperhidrosis (PFH) is a prevalent, mostly hereditary disorder characterized by sweating in excess of what is needed to sustain normal body temperature. PFH can range in severity from mild dampness to severe dripping of certain body areas and can result in a considerable impairment of quality of life. Current treatments available to dermatologists to manage PFH are often inadequate and consist of an amalgamation of topical, oral, or injectable drugs, iontophoresis, thermolysis, or sympathectomies. PFH is recognized as a general autonomic dysfunction with unknown etiology. This disorder relates to overstimulation of the eccrine glands via an autonomic pathway or to an anomalous response to stimuli that raise the basal level of sweat secretion. Since the autonomic nervous system does not function correctly, disabling and pervasive disease symptoms including physiological and psychiatric, can manifest themselves in addition to hyperhidrosis. To start investigating the pathogenesis of PFH, we initiated a large-scale exome-sequencing project consisting of an unprecedented pool of patients and identified mutations in voltage-gated sodium channels as clinically relevant. To probe the involvement of these genes in PFH, we will create a robust animal model in which therapeutics can be tested and by doing so, we expect to generate a first glimpse into possible causes of PFH which, in turn, can help lay the foundation for improving patient quality of life .