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The core of desmosomes is built up of desmosomal cadherins, cadherin\u2010type adhesion molecules that are tethered to intermediate filaments via adaptor proteins of the armadillo and the plakin family. In addition, desmosomal cadherins are present outside of desmosomes. Recent investigations indicate that these molecules are involved in adhesion\u2010dependent and adhesion\u2010independent signaling and thus have functions different from the adhesive properties of their counterparts within desmosomes. Impaired adhesion of desmosomal cadherins both within and outside of desmosomes is the cause of the blistering skin disease pemphigus. Autoantibodies interfere with the binding of desmosomal cadherins and alter intracellular signaling pathways, the latter of which is necessary for loss of cell adhesion. Among the plethora of signaling molecules reported, altered activities of p38MAPK, protein kinase C, and epidermal growth factor receptor (EGFR) are most relevant. 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