Localization of split in PV and PF is explained by the desmoglein compensation hypothesis. In skin (upper panels), Dsg3 is expressed at lower levels of the epidermis, whereas Dsg1 occurs at upper levels. In mucous membranes (lower panels), Dsg3 is present throughout the epidermis, and Dsg1 is present only at upper levels. In skin, anti-Dsg1 induces a split below the granular layer, where Dsg3 is lacking. In the oral mucosa, anti-Dsg3 alone is sufficient to induce suprabasal blisters, since Dsg1 is lacking at lower levels of the epidermis. However, the suprabasal blisters of skin in PV patients are associated with antibodies to both Dsg3 and Dsg1. Figure adapted from Mahoney et al. (7).