Phospholamban (PLN/PLB)

Phospholamban (PLN) is a 52-amino acid integral membrane micropeptide that regulates cardiac muscle contractility and calcium homeostasis by modulating the activity of the sarco(endo)plasmic reticulum Ca2+ ATPase pump (SERCA2). In its unphosphorylated state, PLN inhibits SERCA2, reducing calcium uptake into the sarcoplasmic reticulum. Phosphorylation of PLN at Ser16 or Thr17 relieves this inhibition, increasing calcium uptake and enhancing cardiac muscle relaxation and contraction strength. Mutations in PLN are associated with dilated cardiomyopathy.

Phosphorylation-dependent regulation of SERCA2 activity. Unphosphorylated PLN inhibits SERCA2, while phosphorylated PLN relieves this inhibition, leading to increased Ca2+ uptake into the sarcoplasmic reticulum.