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Plakophilin 2, an armadillo protein, is a constituent of the desmosomal protein complex. Its function is very important in the maintenance of the integrity of tissues exposed to mechanical stress, such as the cardiac tissues. Mutations in the PKP2 gene complex has been implicated in the development of (Arrhythmogenic Cardiomyopathy (ACM), a condition that predisposes athletes to sudden cardiac death, occurring mostly during sporting activities. In this study, we examined the effect of R46K-R125K mutations on the cardiac cells using H9c2 cells. Results show that H9c2 cells bearing mutant (R46K-R125K) gene for PKP2 develop cell hypertrophy after 24 hours, although the mechanisms inducing hypertrophy is currently unknown. However, R46 and R125 are known hotspots for arginine methylation, the authors propose that hypertrophy induction may be associated with factors related to defects in arginine methylation at these sites.