We identified that TMEM43 interacts with lamin B2, and TMEM43‐P386S causes mislocalization of lamin B2 and abnormality in NE structure in ARVC iPSC‐CMs, resulting in decreased chromatin opening of promoters around downregulated genes, including RYR2. This evidence concerns the gene RYR2 and arrhythmogenic right ventricular cardiomyopathy.