Plakophilin-3 (PKP3)

Plakophilin-3 is a member of the armadillo and plakophilin gene families and a critical component of desmosomes, the specialized cell–cell junctions found in epithelial and some other tissues. It is characterized by nine armadillo repeat motifs and localizes both to desmosomes and, in some contexts, to extra-desmosomal cortical regions of polarized cells. Plakophilin-3 links cadherins to intermediate filaments and directly interacts with cytoskeletal proteins such as actin, and has proposed roles in cell signaling, apicobasal polarity, and regulation of cell–cell adhesion. Genetic disruption of PKP3 can lead to dramatic effects on desmosome assembly and positioning, impacting tissue integrity and disease susceptibility, especially in the skin and heart. Plakophilin-3 interacts with major desmosomal cadherins (DSG1, DSG2, DSG3, DSC3) and participates in protein complexes required for cell junction organization. Plakophilin-3 is not currently regarded as a direct therapeutic target, such as a receptor, enzyme, or transporter, but rather a structural and regulatory protein involved in cell–cell adhesion. No drugs are known to directly target or interact with Plakophilin-3 as of current knowledge, and no mechanism of drug action has been described for PKP3, as it is not a drug target. It is not a current clinical biomarker, though alterations, mutations, or expression changes may implicate disease, especially in research. No unique safety concerns are identified related to therapeutic targeting, as it is not a drug target; however, disease mutations may affect cell–cell junction integrity, leading to skin/heart disease.

Other names

PKP3Plakophilin-3plakophilin-3plakophilin 3b