Plakophilin1

Plakophilin-1 (PKP1) is a desmosomal protein encoded by the PKP1 gene in humans. It belongs to the plakophilin family of armadillo repeat-containing proteins that participate in the assembly and function of desmosomes, intercellular junctions that provide strong cell–cell adhesion in tissues subjected to mechanical stress. PKP1 localizes to desmosomal plaques in stratified epithelia, notably the epidermis and mucosal epithelia, where it interacts with desmosomal cadherins (desmogleins and desmocollins) and desmoplakin to organize plaque architecture and link the desmosome to intermediate filaments. Beyond its structural role, plakophilins can influence signaling and, in some contexts, nuclear functions.

Mutations in PKP1 cause inherited skin fragility disorders. Loss-of-function variants are associated with ectodermal dysplasia–skin fragility syndrome, an autosomal recessive condition characterized by increased skin fragility with mechanical trauma, blistering, nail and hair abnormalities, and ichthyosiform features. The phenotype highlights PKP1’s essential role in epidermal desmosomes. PKP1-related disorders are studied to understand desmosomal adhesion and its impact on epithelial integrity.

In research, PKP1 is examined for its interactions with plakoglobin and other plakophilin family members, and for its role in desmosome assembly during epithelial differentiation. Abnormal PKP1 expression or mutations can disrupt desmosomal adhesion, contributing to skin diseases and potentially affecting tissue homeostasis in epithelia.