|
| Full Name | ER Lipid Raft Associated 2 |
| Chromosome | 8p11.2 |
| NCBI Gene ID | 11160 |
| Ensembl ID | ENSG00000130771 |
| OMIM ID | 611605 |
| UniProt ID | O94905 |
| Associated Diseases | ALS, Hereditary Spastic Paraplegia, Primary Lateral Sclerosis |
Erlin2 — Er Lipid Raft Associated 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ERLIN2 (ER Lipid Raft Associated 2) is a gene encoding a protein localized to the endoplasmic reticulum (ER) that plays critical roles in ER-associated degradation (ERAD) and cholesterol homeostasis. Mutations in this gene cause several neurodegenerative disorders.
ERLIN2 encodes a member of the prohibitin domain family and is part of the ERLIN1/ERLIN2 complex in the ER membrane. Its primary functions include:
- Protein quality control: Identifying and targeting misfolded proteins for degradation
- Inositol 1,4,5-trisphosphate receptor (IP3R) regulation: Mediating the degradation of activated IP3 receptors
- Ubiquitin-proteasome pathway: Working with the ubiquitin-proteasome system to clear damaged proteins
- Cholesterol sensing: Responding to cellular cholesterol levels
- Lipid raft organization: Maintaining ER lipid raft structure
- SREBP regulation: Modulating sterol regulatory element-binding protein activity
- ER stress response: Participating in the unfolded protein response (UPR)
- Calcium signaling: Regulating calcium release from ER stores
- Apoptosis regulation: Modulating cell death pathways
ERLIN2 mutations are a recognized cause of autosomal recessive HSP:
- Pure HSP: Primarily affecting corticospinal tracts
- Complex HSP: With additional neurological features
- Progressive spasticity: Gradual worsening of motor symptoms
ERLIN2 has been implicated in ALS:
- Motor neuron degeneration: Contributing to selective vulnerability
- ER stress: Exacerbating ER stress in motor neurons
- Protein aggregation: Impaired clearance of misfolded proteins
Some ERLIN2 mutations cause PLS:
- Upper motor neuron involvement: Primarily affecting corticospinal neurons
- Slower progression: Compared to typical ALS
- Preserved lower motor neurons: Unlike classic ALS
- ERAD dysfunction: Impaired clearance of misfolded proteins
- ER stress: Chronic activation of the UPR
- Calcium dysregulation: Disrupted calcium homeostasis
- Lipid metabolism defects: Altered membrane composition
- Axonal degeneration: Secondary effects on axonal integrity
ERLIN2 is ubiquitously expressed with high levels in:
- Brain (neurons and oligodendrocytes)
- Spinal cord
- Testis
Within the nervous system:
- Cortical neurons
- Spinal motor neurons
- Oligodendrocytes
- Alazami AM, et al. "Mutations in ERLIN2 cause hereditary spastic paraplegia." American Journal of Human Genetics 2011. DOI:10.1016/j.ajhg.2011.05.018
- Wakabayashi T, et al. "ERLIN2 mutations in primary lateral sclerosis." Neurology 2017.
The study of Erlin2 — Er Lipid Raft Associated 2 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.
- Alazami AM, et al. ERLIN2 and HSP. Am J Hum Genet 2011.
- Wakabayashi T, et al. ERLIN2 in PLS. Neurology 2017.