Desmosomes in cardiomyocytes physically hold the cells together, and allow for electrical signaling to propagate through the heart. These structures are also host to signaling proteins (TGF-β1/p38 MAPK) that have been found to be dysregulated in cardiac diseases, such as arrhythmogenic or hypertrophic cardiomyopathy. ASCB members Adi Dubash, Kathleen Green, and colleagues at Northwestern University now show that loss of the desmosomal protein Plakophilin-2 leads to elevated TGF-β1/p38 MAPK, and increased expression of profibrotic genes. However, expression of Desmoplakin, another desmosome protein, can resolve these effects. Published in Journal of Cell Biology.