To uncover potential mechanisms by which TMEM43 mutations may lead to ARVC, we first sought to determine its frequency in the ARVC population by screening for mutations in this gene along with five other desmosomal genes; and we then examined the specific effects of Ser358Leu mutant TMEM43 on stability of desmosomal and nuclear envelope proteins and on gene expression in the COS-7 heterologous cells system. The gene discussed is TMEM43; the disease is arrhythmogenic right ventricular cardiomyopathy.