The skin protects the body from excessive water loss and the invasion of harmful substances, such as chemicals and microbes. The stratum corneum, is recognized as a very important physical barrier. However, in recent years evidence emerged that tight junctions (TJ) might also play a crucial role in barrier function of the skin. TJ consist of transmembrane proteins, e.g. claudins, occludin and junctional adhesion molecules (JAM), and of plaque proteins, e.g. proteins ZO-1, ZO-2, ZO-3, MUPP-1 and symplekin. The molecular composition of TJ is highly complex and varies according to the cell type and degree of differentiation.