Pemphigus is an autoimmune disease of skin adhesion associated with auto-antibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (dsg) 1 and 3 and acetylcholine receptors. Desmogleins, type I membrane proteins, are important for cell adhesion and are expressed in great abundance at the desmosomes, which are adhesive cell junctions. Desmogleins belong to the cadherin family and consist of dsg1, dsg2 and dsg3. Calcium binds to the putative calcium binding sites at the extracellular N-terminal domain, which has cadherin-like repeats. Unlike normal human keratinocytes, the squamous cell carcinoma cells exhibit diminished or un-usual expression of dsg3 and dsg1, which bear pemphigus vulgaris and pemphigus foliaceus antigens, respectively. Several carcinoma cell lines constantly express dsg2 and dsg3 mRNA, whereas cultured normal human keratinocytes always express dsg1 and dsg3 mRNA, with or without dsg2 mRNA. This expression pattern indicates that desmoglein isoforms exhibit abnormal expression and may be related to tumor cell kinetics, such as cell invasion and metastasis. dsg2 is the fundamental dsg common to all desmosome-possessing tissues and is the largest desmoglein in the family.