However, this is not a universal observation, as Siragam et al. [29] showed that overexpression of the TMEM43 S358L mutation in HL-1 cells exhibited reduced CV in monolayers, and other ARVC models exhibit severe clinical phenotypes in the absence of any triggers [30,31]. Here, TMEM43 is linked to arrhythmogenic right ventricular cardiomyopathy.