Gene PKP2
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Also known as
ARVD9, Plakophilin-2Overview
PKP2 (Plakophilin 2) encodes a crucial component of cardiac desmosomes, which are specialized cell-cell junctions that provide mechanical coupling between adjacent heart muscle cells. Plakophilin-2 serves as a key scaffolding protein in desmosomes, linking desmosomal cadherins to intermediate filaments and helping to maintain structural integrity of the heart tissue, particularly during mechanical stress. Beyond its structural role, PKP2 is also involved in intracellular signaling pathways that regulate gene expression and cell differentiation in cardiac tissue.Mutations in PKP2 are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited heart disease characterized by progressive replacement of ventricular myocardium with fibro-fatty tissue. This structural abnormality leads to ventricular arrhythmias and increased risk of sudden cardiac death, particularly in young athletes. ARVC shows variable penetrance and expressivity, with some mutation carriers remaining asymptomatic while others develop severe disease. Genetic testing for PKP2 mutations is important for family screening, risk stratification, and guiding management decisions such as exercise restrictions and implantable cardioverter-defibrillator placement.