📗 Cite This Artifact
ULK2 Gene
ULK2 Gene
Introduction
Ulk2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#4a90d9; color:white;">ULK2 - Unc-51 Like Kinase 2</th></tr>
<tr><td><strong>Full Name</strong></td><td>Unc-51 Like Kinase 2</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>17p11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9716](https://www.ncbi.nlm.nih.gov/gene/9716)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000107485</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q8IYT8](https://www.uniprot.org/uniprot/Q8IYT8)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, ALS</td></tr>
</table>
</div>
Overview
...ULK2 Gene
Introduction
Ulk2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#4a90d9; color:white;">ULK2 - Unc-51 Like Kinase 2</th></tr>
<tr><td><strong>Full Name</strong></td><td>Unc-51 Like Kinase 2</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>17p11.2</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[9716](https://www.ncbi.nlm.nih.gov/gene/9716)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000107485</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q8IYT8](https://www.uniprot.org/uniprot/Q8IYT8)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, ALS</td></tr>
</table>
</div>
Overview
The ULK2 gene encodes Unc-51 Like Kinase 2, a serine/threonine kinase that plays a critical role in the initiation of autophagy. ULK2 is a homolog of yeast Atg1 and is part of the ULK complex that initiates autophagosome formation["@mizushima2010"]. ULK2 is expressed throughout the brain with particularly high levels in regions involved in neurodegeneration, including the [hippocampus](/brain-regions/hippocampus), substantia nigra, and motor [cortex](/brain-regions/cortex)[@lee2011].
Function
ULK2 orchestrates autophagy initiation through a sophisticated cascade of protein interactions and phosphorylation events:
- [Autophagy](/entities/autophagy) initiation: ULK2 complex (ULK1/2, ATG13, FIP200, ATG101) initiates autophagosome formation by recruiting and activating downstream autophagy proteins[@mizushima2010]
- [mTOR](/entities/mtor) sensing: ULK2 is inhibited by mTORC1 under nutrient-rich conditions; mTORC1 phosphorylates ULK2 at multiple sites to suppress autophagy initiation[@egan2011]
- AMPK activation: Energy stress activates AMPK, which directly phosphorylates ULK2 at Ser317 and Ser777 to stimulate autophagy[@gwinn2008]
- Phosphorylation targets: ULK2 phosphorylates multiple autophagy proteins including Beclin-1, Vps34, and ATG14 to promote autophagosome nucleation[@russell2013]
- Neuronal autophagy: Critical for neuronal protein quality control, clearing misfolded proteins and damaged organelles[@button2014]
- Axonal transport: ULK2 localizes to axons and regulates autophagosome formation during axonal transport[@zhou2017]
Structure
ULK2 contains several distinct domains that mediate its function:
Expression Pattern
ULK2 is expressed in:
- Brain tissue ([neurons](/entities/neurons) and glia) - particularly high in hippocampus CA1 neurons and Purkinje cells
- Various tissues with high metabolic activity including heart, liver, and skeletal muscle
- Localizes to cytoplasm and punctate structures corresponding to phagophores
- Expressed in both excitatory and inhibitory neurons
Disease Associations
Alzheimer's Disease
- ULK2-mediated autophagy clears [Aβ](/proteins/amyloid-beta) plaques; reduced ULK2 activity contributes to [Aβ](/proteins/amyloid-beta) accumulation[@boland2008]
- Impaired autophagy in AD neurons correlates with cognitive decline
- mTOR hyperactivation in AD inhibits ULK2, creating a double burden on protein clearance
- ULK2 deficiency in mouse models leads to increased Aβ deposition and memory deficits[@boland2008]
- Therapeutic strategies aim to activate ULK2 through AMPK activation or mTOR inhibition
Parkinson's Disease
- ULK2 in mitophagy initiation; PINK1/Parkin pathway requires ULK2 for autophagosome formation[@lazarou2015]
- Clearance of damaged mitochondria is critical for dopaminergic neuron survival
- [α-synuclein](/proteins/alpha-synuclein) clearance via ULK2-mediated selective autophagy
- LRRK2 mutations affect ULK2 localization and function
- ULK2 activators are being explored as disease-modifying therapies
ALS
- Autophagy initiation defects contribute to protein aggregate accumulation in ALS[@wong2015]
- ULK2 in aggregate clearance; mutant SOD1 and FUS inclusions require ULK2 for removal
- Mutations in ULK2 have been identified in some ALS patients
- Therapeutic targeting aims to enhance autophagy initiation
Therapeutic Implications
ULK2 represents a promising therapeutic target for neurodegenerative diseases:
| Therapeutic Approach | Mechanism | Development Stage | References |
|---------------------|-----------|-------------------|------------|
| Small molecule ULK2 activators | Direct activation of ULK2 kinase | Preclinical | [@egan2011a] |
| AMPK activators (metformin, AICAR) | Indirect ULK2 activation via AMPK | Clinical trials for AD/PD | [@steinbaum2014] |
| mTOR inhibitors (rapamycin, everolimus) | Disinhibition of ULK2 | Approved for other conditions | [@bove2011] |
| Gene therapy | Viral delivery of ULK2 | Preclinical | [@zhang2017] |
Research Directions
Current research focuses on:
Animal Models
Several animal models have been developed to study ULK2:
- ULK2 knockout mice: Viable with subtle phenotypes, suggesting compensation by ULK1
- ULK1/ULK2 double knockout: Embryonic lethal, demonstrating essential function
- Conditional knockout models: Brain-specific deletion shows neurodegeneration phenotypes
- knock-in models: Expressing phosphodeficient or phosphomimetic ULK2 mutants
Key Publications
See Also
- [ULK2 Protein](/proteins/ulk2-protein)
- [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosomal-pathway)
- [AMPK Signaling Pathway](/mechanisms/ampk-signaling-pathway)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyotrophic Lateral Sclerosis](/diseases/als)
External Links
- [NCBI Gene: ULK2](https://www.ncbi.nlm.nih.gov/gene/9716)
- [UniProt: Q8IYT8](https://www.uniprot.org/uniprot/Q8IYT8)
- [Ensembl: ULK2](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000107485)
Background
The study of Ulk2 Gene 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.
References
Pathway Diagram
The following diagram shows the key molecular relationships involving ULK2 Gene discovered through SciDEX knowledge graph analysis:
▸Metadataorigin_type: v1_polymorphic_backfill
| slug | genes-ulk2 |
| kg_node_id | ULK2 |
| entity_type | gene |
| origin_type | v1_polymorphic_backfill |
| source_table | wiki_pages |
| wiki_page_id | wp-3589a297a775 |
| __merged_from | {'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ulk2'} |
| _schema_version | 1 |
No provenance edges found
Use ?embed=1 to load the artifact without SciDEX chrome — suitable for iframing into wiki pages or external sites.
<iframe src="http://scidex.ai/artifact/wiki-genes-ulk2?embed=1" width="100%" height="600" style="border:0;border-radius:8px"></iframe>
[ULK2 Gene](http://scidex.ai/artifact/wiki-genes-ulk2)
http://scidex.ai/artifact/wiki-genes-ulk2