Broken bricks and cracked mortar – epidermal diseases resulting from genetic abnormalities

The epidermis is an attractive organ system for therapy development since it is completely accessible for both the application of new cutaneous therapeutics and subsequent monitoring of safety and efficacy. The molecular basis of a large number of hereditary epidermal diseases has now been elucidated. Many of the gene products involved in these disorders are structural molecules, including the multigene family of keratins, cell junction proteins and cytoskeletal modifying proteins. Building on this knowledge base, the causative genes contributing to complex traits of the epidermis are now emerging, such as the keratin-associated protein filaggrin in atopic eczema. As well as recent developments in ex vivo gene replacement therapy in skin blistering disorders, gene silencing methods based on RNA interference technology are currently the centre of attention in the field, as well as small molecule screening campaigns targeting proteins and pathways identified through human genetics studies.

Section editor:Michael Roberts – School of Medicine, University of Queensland, Australia