Desmosomes are found in all epithelial cells and some specific tissues. They are mainly composed of two classes of proteins, i.e., transmembrane proteins and intracytoplasmic proteins. The structural destruction of some kinds of desmosomal proteins can lead to skin diseases of different severity. It has been demonstrated that desmosomes are predominantly associated with autoimmune skin diseases such as pemphigus, genodermatosis conditions and staphylococcal scalded skin syndrome. This article outlines the molecular structures of desmosomal proteins as well as the pathogenesis of skin diseases caused by the abnormalities of desmosomal proteins.