From mutation to arrhythmia: Desmosomal protein breakdown as an underlying mechanism of cardiac disease

Mutations in genes that form the desmosome are the most common cause of the cardiac disease arrhythmogenic cardiomyopathy (ACM), which affects one in 2000 to 5000 people worldwide. Researchers have now discovered how a mutation in the desmosomal gene plakophilin-2 leads to ACM. They found that the structural and functional changes in ACM hearts caused by a plakophilin-2 mutation are the result of increased desmosomal protein degradation. The results further our understanding of ACM and could contribute to the development of new therapies for this disease.