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Target intelligence / Profile preview
Phospholamban (PLN/PLB)
- Target
- PLN/PLB
- Molecular classification
- Micropeptide, SERCA regulator
01
Overview
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.
02
Mechanism of action
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.
03
Biological functions
Regulation of cardiac muscle contractilityRegulation of calcium homeostasisRegulation of SERCA2 activity
04
Disease associations
Dilated cardiomyopathyCongestive heart failure
05
Safety considerations
Mutations in PLN can cause inherited dilated cardiomyopathy.
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