PKP1 Gene

Plakophilins belong to the so-called Armadillo proteins. "Armadillo" refers to a characteristic, repetitive sequence of amino acids (Armadillo repeat). This was first discovered in Drosophila (fruit fly). Armadillo proteins include plakophilins, beta-catenin, alpha-importin and others.

Plakophilins regulate plaque organization and keratin filament anchoring in desmosomes. Plakophilins are expressed in a cell type-specific manner.

Plakophilin 1 was first described as a keratin-binding protein and stabilizes desmosomal proteins and keratins at the plasma membrane.

Plakophilins 2 and 3 show a broader expression patternand are also expressed in simple epithelia. For example, plakophilin 2 is also found in the cell contacts of the smooth strips in cardiac muscle cells. Mutations in the plakophilin 2 gene results in familial cardiomyopathy. Plakophilin 2 is overexpressed in various tumors. Tumors so in gliomas (Zhang et al. 2017).

Mutations in the PKP1 gene, which encodes plakophilin 1, cause "ectodermal dysplasia/skin fragility syndrome" in humans, a skin disease with palmoplantar keratosis, traumatically induced blistering, reduced intercellular adhesion and woolly hair(frizzy hair). The number, size and stability of desmosomes are reduced and keratin anchorage is disturbed. In addition, keratin aggregates are formed in the cytoplasm.