LRP5 Protein

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LRP5 Protein

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LRP5 Protein

Introduction

Lrp5 Protein 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-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">LRP5 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Low-density lipoprotein receptor-related protein 5</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>LRP5</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[4041](https://www.ncbi.nlm.nih.gov/gene/4041)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[O75177](https://www.uniprot.org/uniprot/O75177)</td></tr>
<tr><td><strong>MW</strong></td><td>179 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cell membrane, Endosomes</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/autosomal-dominant-polycystic-kidney-diseases" style="color:#ef9a9a">Autosomal Dominant Polycystic Kidney Diseases</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">67 edges</a></td>
</tr>
</table>
</div>

Overview

...

LRP5 Protein

Introduction

Lrp5 Protein 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-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">LRP5 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Low-density lipoprotein receptor-related protein 5</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>LRP5</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[4041](https://www.ncbi.nlm.nih.gov/gene/4041)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[O75177](https://www.uniprot.org/uniprot/O75177)</td></tr>
<tr><td><strong>MW</strong></td><td>179 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cell membrane, Endosomes</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/autosomal-dominant-polycystic-kidney-diseases" style="color:#ef9a9a">Autosomal Dominant Polycystic Kidney Diseases</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">67 edges</a></td>
</tr>
</table>
</div>

Overview

Mermaid diagram (expand to render)

LRP5 (Low-density lipoprotein receptor-related protein 5) is a member of the LDL receptor family that functions as a co-receptor for Wnt/beta-catenin signaling["@he2004"]. Originally characterized for its role in bone mass regulation, LRP5 is also expressed in the central nervous system where it plays important roles in neuronal development, synaptic plasticity, and cognitive function["@gong2001"]. LRP5 variants have been associated with Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders.

Molecular Function

Wnt Co-receptor Function

LRP5 serves as a critical Wnt co-receptor:

Wnt binding: Binds Wnt ligands (Wnt1, Wnt3, Wnt3a, Wnt5a)
Frizzled interaction: Forms receptor complexes with Frizzled proteins
β-catenin stabilization: Initiates canonical Wnt/β-catenin signaling
Signal modulation: Regulates downstream gene transcription

Lipoprotein Receptor Function

As an LDL receptor family member:

Lipoprotein binding: Binds various lipoproteins
Endocytosis: Mediates uptake of ligands
LRP6: Closely related paralog with overlapping functions

Neuronal Functions

In [neurons](/entities/neurons) and synapses:

Synaptic plasticity: Regulates hippocampal [long-term potentiation](/mechanisms/long-term-potentiation) (LTP)
Cognitive function: Important for learning and memory
Neurogenesis: Affects neural progenitor cell function
Dendritic spine morphology: Regulates spine density and shape

Disease Associations

Alzheimer's Disease

LRP5 is genetically and functionally linked to AD[@de2007]:

| Variant | Effect | Association |
|---------|--------|-------------|
| p.A1330V | Gain of function | Reduced AD risk |
| p.S371L | Altered function | Increased risk |
| Expression | Reduced in AD brain | Pathogenic |

Mechanisms:

Wnt/β-catenin signaling impairment
Synaptic dysfunction
[Aβ](/proteins/amyloid-beta) interactions

Parkinson's Disease

GWAS associations: LRP5 variants linked to PD risk
Dopaminergic function: Affects dopamine neuron survival
LRP6 connection: Shared pathways with LRP5

Bone Disorders

High bone mass: Gain-of-function mutations
Osteoporosis-pseudoglioma: Loss-of-function mutations

Pathway Interactions

Wnt/β-Catenin Signaling

LRP6: Functional paralog and co-receptor[@macdonald2009]
DVL: Dishevelled downstream of LRP5
GSK3β: Inhibited by Wnt signaling
β-catenin: Stabilized and translocates to nucleus

Synaptic Signaling

PSD-95: Postsynaptic density protein
NMDA receptors: Interaction with synaptic proteins
AMPA receptors: Regulates trafficking

Lipid Metabolism

[Apolipoprotein E](/proteins/apoe): LRP5 interacts with ApoE
Cholesterol: May affect neuronal cholesterol homeostasis
[Amyloid precursor protein](/entities/app-protein): APP processing interactions

Therapeutic Implications

Wnt Pathway Modulators

LRP5 agonists: Wnt pathway activators
Small molecule Wnt activators: e.g., CHIR99021
LRP5/LRP6 bifunctional agents: In development

Targeting LRP5 for Neurodegeneration

[Blood-brain barrier](/entities/blood-brain-barrier): Challenge for CNS delivery
Peripheral modulation: May affect central Wnt signaling
Combination approaches: With other pathway modulators

Background

The study of Lrp5 Protein 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.

Pathway Diagram

The following diagram shows the key molecular relationships involving LRP5 Protein discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

LRP5

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slug	proteins-lrp5
kg_node_id	LRP5
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-13a46cadf442
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-lrp5'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

80%

Debates

0

Incoming

16

Outgoing

38

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

LRP5 Protein

LRP5 Protein

Introduction

Overview

LRP5 Protein

Introduction

Overview

Molecular Function

Wnt Co-receptor Function

Lipoprotein Receptor Function

Neuronal Functions

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Bone Disorders

Pathway Interactions

Wnt/β-Catenin Signaling

Synaptic Signaling

Lipid Metabolism

Therapeutic Implications

Wnt Pathway Modulators

Targeting LRP5 for Neurodegeneration

Background

See Also

Pathway Diagram

💬 Discussion