Apremilast improves cardiomyocyte cohesion and arrhythmia in different models for arrhythmogenic cardiomyopathy

• Apremilast rescues loss of cardiomyocyte cohesion in human iPSC-derived cardiomyocytes from an ACM patient with a DSP mutation. • Apremilast enhances cardiomyocyte cohesion via plakoglobin phosphorylation at Serine 665 and ERK1/2 activation. • Apremilast reduces arrhythmic events in ex vivo and in vitro models of ACM, including ventricular slices and Langendorff-perfused hearts. • This study provides preclinical evidence for apremilast as a potential targeted therapy for arrhythmogenic cardiomyopathy.