plakophilins

Plakophilins are a family of desmosomal plaque proteins belonging to the armadillo repeat-containing protein family. The human plakophilin family includes three members, PKP1, PKP2, and PKP3, encoded by PKP1, PKP2, and PKP3 genes. They localize to desmosomes in adherent cell junctions and participate in linking desmosomal cadherins to the intermediate filament cytoskeleton. As components of the desmosomal plaque, plakophilins cooperate with desmogleins and desmocollins, desmoplakin, and other plaque proteins to support tissue integrity in mechanically stressed epithelia and cardiac muscle.

Structure and function: Plakophilins contain armadillo repeat domains that mediate protein-protein interactions. They contribute to desmosome assembly and stability by promoting plaque organization and lateral adhesion. PKP1 is enriched in stratified epithelia such as skin and mucosa; PKP2 is widely expressed, with notable expression in heart; PKP3 is more broadly distributed and can be present in many epithelial and mesenchymal tissues. The plakophilins also participate in dynamic remodeling of desmosomes during development, wound healing, and tissue turnover.

Clinical relevance: Mutations in PKP genes have been associated with human disease. PKP1 mutations underlie skin fragility syndromes, including ectodermal dysplasia with palmoplantar keratoderma. PKP2 mutations are a major cause of arrhythmogenic right ventricular cardiomyopathy, a heritable heart disease that predisposes to sudden cardiac death. The disease associations for PKP3 are less clearly defined, with research ongoing.

See also: desmosome, armadillo repeat proteins, desmoplakin, desmoglein, desmocollin.