Plakophilins 1, 2, 3 and 4 (PKP1-4) influence development and participate in linking cadherins to cytoskeletal intermediate filaments. Plakophilins 1-4 contain arm-repeat (armadillo) domains, and localize to nuclei and cell desmosomes (cell-cell junctions found in suprabasal layers of stratifying epithelia that undergo mechanical stress). Plakophilin-1 mediates increases in desmosomal protein content, desmosome assembly, and regulation of cell migration. Plakophilin-2 is important for desmosome assembly and is an essential morphogenic factor and architectural component of the heart. Plakophilin-3 plays a role in both desmosome-dependent adhesion and signaling pathways. Plakophilin-4 is a component of desmosomal adhesion plaques that regulates junctional plaque organization and cadherin function.