Our primary research goal is to identify pathogenetic mechanisms underlying genodermatoses (hereditary disorders of the skin and its appendages) at a molecular level and to develop appropriate therapeutic approaches. These diseases are rare, but may be associated with life-threatening complications already in the first weeks after birth. In addition to the skin, other organs, such as eye, ear, and lung, are frequently affected by pathogenetic processes. First systematic studies of patients of different age groups allowed the characterization of genotype-phenotype relationships as a prerequisite for specific therapeutic attempts. In mouse models of epidermolysis bullosa, lamellar ichthyosis, and hypohidrotic ectodermal dysplasia, we have been investigating the feasibility of gene therapy in utero or perinatal protein replacement therapy. In September 2013 we started the first clinical trial in neonates with hypohidrotic ectodermal dysplasia, a multicenter interventional study based on the promising preclinical data collected over the last years.