Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that is associated with underlying neoplasms. PNP sera react with multiple plakin family proteins, among which only envoplakin and periplakin are constantly detected. Envoplakin, a membrane-associated precursor of the epidermal cornified envelope and desmosomes, is a member of the plakin family of proteins. Envoplakin is expressed in epidermal and esophageal keratinocytes and nonepithelial stratified squamous epithelia, but not in simple epithelia or nonepithelial cells. Envoplakin co-localizes with desmoplakin at desmosomes and on keratin filaments throughout the differentiated layers of the epidermis, but mainly accumulates in nuclear and cytoplasmic aggregates with associated intermediate filaments. The envoplakin rod domain is required for aggregation and the linker domain is required for intermediate filament association. The distribution of envoplakin at the interdesmosomal plasma membrane depends on heterodimerization with periplakin
