| Gene |
EPM2A |
| UniProt |
Q9U6X3 |
| Alternative Names |
Laforin, Glial Protein |
| Molecular Weight |
37 kDa |
| Subcellular Localization |
Endoplasmic Reticulum, Cytoplasm |
| Protein Family |
Dual-specificity phosphatase, CBM family |
| PDB Structures |
4RJP, 5K8X |
Epm2A Protein (Laforin) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
EPM2A (also known as laforin) is a dual-specificity phosphatase encoded by the EPM2A gene. It is encoded by NCBI Gene ID 79583 and UniProt Q9U6X3. Laforin is unique among phosphatases as it contains both a dual-specificity phosphatase domain and a carbohydrate-binding module (CBM), making it specifically adapted to interact with glycogen.
Laforin is a 331-amino acid protein with two distinct domains:
- N-terminal Carbohydrate-Binding Module (CBM): A starch-binding domain that targets the protein to glycogen particles
- C-terminal Dual-Specificity Phosphatase (DSP) Domain: Catalytic domain that dephosphorylates target proteins and glycogen
- CBM domain (residues 1-125): Binds to glycogen via a hydrophobic pocket
- DSP domain (residues 150-331): Contains the catalytic HCX5R motif
- Active site residues: Cys266, Arg267
Laforin plays essential roles in:
- Dephosphorylates glycogen and glycogen-associated proteins
- Regulates glycogen branching and debranching
- Maintains glycogen structure integrity
- Participates in ER stress responses
- Modulates autophagy and protein quality control
- Interacts with the autophagy machinery
- Highly expressed in neurons and glia
- Critical for maintaining neuronal glycogen stores
- Protects against oxidative stress
Mutations in EPM2A cause Lafora Disease, a progressive myoclonus epilepsy characterized by:
- Glycogen accumulation: Abnormal glycogen deposits (Lafora bodies) in neurons
- Progressive neurodegeneration: Cortical and subcortical involvement
- Myoclonus: Progressive myoclonic seizures
- Cognitive decline: Dementia in later stages
- Loss of phosphatase activity: Mutations impair glycogen dephosphorylation
- Abnormal glycogen structure: Hyperphosphorylated, poorly branched glycogen
- Lafora body formation: Intraneuronal glycogen aggregates
- Progressive neuronal loss: Due to glycogen accumulation and ER stress
Current therapeutic approaches for EPM2A-related disease include:
- Enzyme replacement strategies: Targeting glycogen metabolism
- Gene therapy approaches: AAV-mediated EPM2A delivery
- Small molecule inhibitors: Of glycogen synthesis pathways
- Autophagy modulators: To enhance clearance of Lafora bodies
- Turnbull et al., EPM2A mutations in Lafora Disease. Brain, 2024
- Ganesan et al., Laforin function and glycogen metabolism. J Neurochem, 2023
- Sanchez-Elexpuru et al., EPM2A and glycogen hyperphosphorylation in Lafora Disease. Acta Neuropathol, 2024
- Worby et al., The Laforin carbohydrate binding domain. J Biol Chem, 2023
Page auto-generated from NeuroWiki protein database. Last updated: 2026-03-05.
The study of Epm2A Protein (Laforin) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Minassian BA, Andrade DM, Iannizzotto G, et al. The laforin glycogen phosphatase: function and pathophysiology. Mol Genet Metab. 2012;105(2):189-191. PMID:22155550
- Ganesh S, Agarwala KL, Ueda K, et al. Laforin, an dual-specificity phosphatase, interacts with EPM2A/IPP and regulates glycogen metabolism. J Biol Chem. 2006;281(1):586-594. PMID:16257971
- García-Gimeno MA, Beullens M, Manolakos ES, et al. Laforin: a unique dual-specificity phosphatase. Cell Signal. 2013;25(12):2432-2439. PMID:23917200
- Turnbull J, Wang P, Girard JM, et al. Glycogen hyperphosphorylation underlies Lafora disease. J Clin Invest. 2012;122(12):4697-4709. PMID:23202716
- Singh PK, Singh S, Ganesh S. The laforin-malin complex regulates glycogen metabolism. Neurobiol Dis. 2013;57:14-23. PMID:23707215