PLN encodes phospholamban, a critical regulator of calcium handling in cardiac and skeletal muscle. While primarily studied in cardiovascular disease, calcium dysregulation is a key feature of neurodegenerative diseases, making PLN relevant to neurodegeneration research.
PLN (Phospholamban) is a small phosphoprotein that regulates the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). It is predominantly expressed in cardiac and skeletal muscle, but calcium handling mechanisms involving PLN are also important in neurons where calcium dysregulation is a hallmark of neurodegeneration.
| Property |
Value |
| Gene Symbol |
PLN |
| Full Name |
Phospholamban |
| Chromosomal Location |
6q22.1 |
| NCBI Gene ID |
5350 |
| OMIM ID |
172090 |
| Ensembl ID |
ENSG00000160072 |
| UniProt ID |
P26678 |
| Encoded Protein |
Phospholamban |
| Associated Diseases |
Dilated cardiomyopathy, neurodegenerative diseases (calcium dysregulation), sarcopenia |
Phospholamban regulates calcium reuptake into the sarcoplasmic reticulum:
- Inhibits SERCA1 (skeletal muscle) and SERCA2 (cardiac muscle)
- Phosphorylation (by PKA, CaMKII) relieves inhibition
- Regulates muscle contraction and relaxation
- Critical for calcium homeostasis in muscle cells
- SERCA pumps are expressed in neurons
- Calcium dysregulation is a key feature of AD, PD, ALS
- PLN-related signaling pathways affect neuronal calcium
- ER stress involves calcium handling disruptions
- β-adrenergic signaling → PKA → PLN phosphorylation
- Calcium/calmodulin-dependent protein kinase II (CaMKII)
- Protein phosphatase 1 (PP1) - dephosphorylates PLN
- Calcium dysregulation is an early feature of AD
- ER calcium handling is impaired in neurons
- SERCA dysfunction contributes to amyloid toxicity
- Phosphorylation pathways are altered
- Dopaminergic neurons have high calcium demands
- Calcium influx contributes to mitochondrial stress
- SERCA activity is reduced in PD models
- Calcium overload leads to cell death
- Motor neurons are particularly calcium-sensitive
- Calcium dysregulation contributes to excitotoxicity
- Impaired ER calcium handling in ALS models
PLN has tissue-specific expression:
- Highest expression: Heart (cardiac muscle)
- High expression: Skeletal muscle (slow-twitch fibers)
- Moderate expression: Brain (certain regions)
- Cellular localization: Sarcoplasmic reticulum membrane
In the brain:
- Lower expression than in muscle
- Detected in some neuronal populations
- May play role in neuronal ER calcium regulation
- MacLennan & Kranias, Phospholamban: a crucial regulator of cardiac contractility (2003)
- Kaurstad et al., Phospholamban and calcium handling in disease (2012)
- Berridge, Calcium signalling in neurodegeneration (2010)
- Mattson, Calcium and neurodegeneration (2007)