Defects in Ca2+ signaling linked to stress-induced remodeling that results in leaky RyR channels have been implicated in heart failure (Dridi et al., 2020c; Marks, 2003), cardiac arrhythmias (Dridi et al., 2020c; Lehnart et al., 2006; Lehnart et al., 2004; Vest et al., 2005; Wehrens et al., 2003), diabetes (Santulli et al., 2015), muscle weakness (Kushnir et al., 2020; Dridi et al., 2020b; Matecki et al., 2016; Dridi et al., 2020d), and neurodegenerative disorders (Dridi et al., 2020b; Lacampagne et al., 2017; Liu et al., 2012). This evidence concerns the gene RYR1 and heart failure.