Since the study by Marx et al. (2000) reporting that S2808 was hyperphosphorylated in heart failure patients and that its phosphorylation enhanced dramatically the activity of RyR2 channels, several groups have studied this phospho-site in detail (Jiang et al., 2002; Rodriguez et al., 2003; Stange et al., 2003; Currie et al., 2004; Ai et al., 2005; Xiao et al., 2005; Carter et al., 2006; Kohlhaas et al., 2006; Huke and Bers, 2008; MacDonnell et al., 2008; Fischer et al., 2013), with the majority of evidence pointing to S2808 being a target for PKA, CaMKII and possibly PKG. This evidence concerns the gene CAMK2G and heart failure.