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A major cause of morbidity among affected infants is severe and chronic skin erosions. Currently, supportive care is the only available treatment option for AEC patients. Mutations in <jats:italic>TP63<\/jats:italic>, a gene that encodes key regulators of epidermal development, are the genetic cause of AEC. However, it is currently not clear how mutations in <jats:italic>TP63<\/jats:italic> lead to the various defects seen in the patients' skin. In this review, we will discuss current knowledge of the AEC disease mechanism obtained by studying patient tissue and genetically engineered mouse models designed to mimic aspects of the disorder. We will then focus on new approaches to model AEC, including the use of patient cells and stem cell technology to replicate the disease in a human tissue culture model. The latter approach will advance our understanding of the disease and will allow for the development of new in vitro systems to identify drugs for the treatment of skin erosions in AEC patients. Further, the use of stem cell technology, in particular induced pluripotent stem cells (iPSC), will enable researchers to develop new therapeutic approaches to treat the disease using the patient's own cells (autologous keratinocyte transplantation) after correction of the disease\u2010causing mutations. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36455","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T02:52:56Z","timestamp":1395715976000},"page":"2443-2454","source":"Crossref","is-referenced-by-count":19,"title":["Modeling AEC\u2014New approaches to study rare genetic disorders"],"prefix":"10.1002","volume":"164","author":[{"given":"Peter J.","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Colorado School of Medicine Aurora Colorado"},{"name":"Department of Cell and Developmental Biology University of Colorado School of Medicine Aurora Colorado"},{"name":"Charles C. 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