For instance, chronic “hyper-phosphorylation” of RyR2 by PKA (Marx et al., 2000) and CaMKII (Ai et al., 2005; Curran et al., 2010; Grimm et al., 2015; Pereira et al., 2017) that occurs in HF causes dissociation of FKBP12.6 from RyR2, destabilizes the RyR2 complex and causes functional uncoupling of neighboring RyRs. This evidence concerns the gene RYR2 and hydrops fetalis.