Phospholamban (PLB or PLN) pentameric Ca²⁺/K⁺ channel (Kovacs et al., 1988; Smeazzetto et al. 2013; Smeazzetto et al. 2014).  In spite of extensive experimental evidence, suggesting a pore size of 2.2 Å, the conclusion of ion channel activity for phospholamban has been questioned (Maffeo and Aksimentiev 2009).  Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca²⁺ ATPase (SERCA). This cyclic mechanism constitutes the driving force for calcium reuptake from the cytoplasm into the myocyte lumen, regulating cardiac contractility. PLN undergoes a conformational transition between a relaxed (R) and tense (T) state, an equilibrium perturbed by the addition of SERCA. Phosphoryl transfer to Ser16 induces a conformational switch to the R state. The binding affinity of PLN to SERCA is not affected ((K_d ~ 60 μM). However, the binding surface and dynamics in domain Ib (residues 22-31) change substantially upon phosphorylation. Since PLN can be singly or doubly phosphorylated at Ser16 and Thr17, these sites may remotely control the conformation of domain Ib (Traaseth et al. 2006). Phospholamban interests with SERCA with conformational memory (Smeazzetto et al. 2017). Under physiological conditions, PLB phosphorylation induces little or no change in the interaction of the TMS with SERCA, so relief of inhibition is predominantly due to the  structural shift in the cytoplasmic domain (Martin et al. 2018). The phospholamban pentamer alters the function of the sarcoplasmic reticulum calcium pump, SERCA (Glaves et al. 2019). PLB phosphorylation serves as an allosteric molecular switch that releases inhibitory contacts and strings together the catalytic elements required for SERCA activation (Aguayo-Ortiz and Espinoza-Fonseca 2020).