RYR2 and heart failure: At a systemic level of regulation, the association of FKBP12.6 with the tetrameric macromolecular RyR2 channel complex is especially thought to serve as a potential therapeutic strategy against heart failure (Yano et al, 2003) because enhanced binding reduced, whereas diminished binding increased RyR2-mediated Ca2+ leak, the latter being affected by PKA-mediated phosphorylation of RyR2 during β-adrenergic stimulation (Marx et al, 2000; Marx & Marks, 2013).