Plakoglobin is a major cytoplasmic component of both desmosomes and adherens junctions, and is the only known constituent common to submembranous plaques in both of these structures,[9] which are located at the intercalated disc (ICD) of cardiomyocytes.

Transgenic mice homozygous for a null mutation of the JUP gene die around embryonic day 12 from substantial defects in adherens junctions and a lack of functional desmosomes in the heart.

[12][13] Further studies showed that cardiac fibers obtained from JUP-null embryonic mice had decreased passive compliance albeit normal attachment of sarcomeres to adherens junctions.

Transgenic mice displayed a similar phenotype as arrhythmogenic right ventricular cardiomyopathy patients, with loss of cardiomyocytes, fibrosis and cardiac dysfunction, as well as alterations in desmosome protein content and gap junction remodeling.

Mice exhibited cardiomyopathy, fibrosis, conduction abnormalities and sudden cardiac death, presumably via spontaneous lethal ventricular arrhythmias.

Phosphorylation of N-terminal Serines by a “destruction complex” composed of glycogen synthase kinase 3β (GSK3β) and scaffold proteins adenomatous polyposis coli (APC) and axin targets plakoglobin for degradation.[18][19][20][31–33].

Affected individuals have kinky, wooly hair; there is also palmar and plantar erythema at birth that progresses to keratosis as the palms and soles of the feet are used in crawling and walking.