CaM binding may hinder direct Ca2+ modulation, causing a negative shift in Nav1.5 channels’ steady-state inactivation curve and affecting their function.5,6,8–10 Previous studies using genetically engineered co-expression models of LQTS-CaM pathogenic variants and Nav1.5 have revealed the inconsistent role of Nav1.5 channels in pathogenesis. This evidence concerns the gene CALM3 and familial long QT syndrome.