Desmosomes are intercellular adhesive junctions of epithelial cells. They also participate in signal transduction and cell differentiation. Biochemically the following main desmosomal proteins have been identified and characterized: desmogleins, desmocollins, plakoglobin, desmoplakins and plakophilins. Desmosomal cadherins form calcium-dependent adhesion between the neighbouring keratinocytes. The cytoplamic domain of desmogleins and desmocollins interact with plakoglobin which in turn binds to desmoplakin. Desmoplakin finally is anchored to the intermediate filament cytoskeleton. Desmosomes are implicated in pathophysiological mechanisms of autoimmune diseases, genetic diseases and infectious skin diseases.