“…While the primary kinases implicated in phosphorylation of RyR2 have been well established, the nature of the specific phosphatase(s) responsible for dephosphorylating each site in vivo, until now, was less clear. In this issue of the Journal of Physiology, Potenza et al (2020) establish protein phosphatase 1 (PP-1) as an endogenous regulator of RyR2 phosphorylation at one of these key sites. They additionally demonstrate that excessive dephosphorylation of RyR2 by PP-1, much like excessive phosphorylation, results in enhanced calcium leak, further supporting the idea that RyR2 requires an intermediate level of phosphorylation to function correctly.…”