Flotillin-1 Protein

Migration, Crosslink

📖

Flotillin-1 Protein

active

wiki page Created: 2026-04-02T07:19:08 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-flotillin-1-protein

📖 Wiki Page

protein3155 wordssynced 2026-04-02

Flotillin-1 Protein

Overview

Flotillin-1 (FLOT1) is a lipid raft-associated protein belonging to the SPFH (Stomatin/Prohibitin/Flotillin/HflC/K) protein family. Originally identified as a marker of lipid rafts—dynamic membrane microdomains enriched in cholesterol and sphingolipids—flotillin-1 has emerged as a multifunctional scaffolding protein that organizes signaling complexes, regulates membrane protein trafficking, and modulates synaptic function. The protein forms hetero-oligomeric complexes with flotillin-2 and localizes to specialized membrane domains in various cell types, including neurons and glial cells in the central nervous system [@morrow2002][@stefani2011].

In neurodegeneration, flotillin-1 plays complex roles at the intersection of lipid metabolism, protein aggregation, and neuroinflammation. The protein influences amyloid precursor protein (APP) processing and amyloid-beta generation in Alzheimer's disease, regulates alpha-synuclein aggregation in Parkinson's disease, and contributes to membrane alterations in amyotrophic lateral sclerosis (ALS). Its strategic localization to lipid rafts positions flotillin-1 at key sites where pathological protein aggregation and signaling dysregulation occur in neurodegenerative conditions [@banerjee2010][@su2008].

...

Flotillin-1 Protein

Overview

Flotillin-1 (FLOT1) is a lipid raft-associated protein belonging to the SPFH (Stomatin/Prohibitin/Flotillin/HflC/K) protein family. Originally identified as a marker of lipid rafts—dynamic membrane microdomains enriched in cholesterol and sphingolipids—flotillin-1 has emerged as a multifunctional scaffolding protein that organizes signaling complexes, regulates membrane protein trafficking, and modulates synaptic function. The protein forms hetero-oligomeric complexes with flotillin-2 and localizes to specialized membrane domains in various cell types, including neurons and glial cells in the central nervous system [@morrow2002][@stefani2011].

In neurodegeneration, flotillin-1 plays complex roles at the intersection of lipid metabolism, protein aggregation, and neuroinflammation. The protein influences amyloid precursor protein (APP) processing and amyloid-beta generation in Alzheimer's disease, regulates alpha-synuclein aggregation in Parkinson's disease, and contributes to membrane alterations in amyotrophic lateral sclerosis (ALS). Its strategic localization to lipid rafts positions flotillin-1 at key sites where pathological protein aggregation and signaling dysregulation occur in neurodegenerative conditions [@banerjee2010][@su2008].

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Flotillin-1 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Flotillin-1</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>FLOT1</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[O75955](https://www.uniprot.org/uniprot/O75955)</td></tr>
<tr><td><strong>Alternative Names</strong></td><td>Reggae-1, REGI, FLOT1</td></tr>
<tr><td><strong>Protein Family</strong></td><td>SPFH protein family</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>47.5 kDa (427 amino acids)</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Plasma membrane, lipid rafts, endosomes</td></tr>
<tr><td><strong>Chromosomal Location</th><td>6p21.1</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Structure

Domain Architecture

Flotillin-1 is a ~427 amino acid protein with a distinctive domain structure:

SPFH Domain (N-terminal): The N-terminal region (~80 amino acids) contains the SPFH domain, which is shared with other SPFH family members. This domain is critical for:
Oligomerization (forming higher-order complexes)
Lipid raft targeting and localization
Protein-protein interactions within the membrane
Flotillin Domain (C-terminal): The C-terminal region (~300 amino acids) comprises the conserved "flotillin" domain of unknown function. This domain:
Mediates protein-lipid interactions
Contributes to complex formation
May have scaffolding properties
Transmembrane Regions: Unlike typical integral membrane proteins, flotillin-1 associates with the inner leaflet of the plasma membrane through lipid modifications and protein-protein interactions rather than spanning the membrane.

Oligomerization

Flotillin-1 forms both homo-oligomers and hetero-oligomers with flotillin-2. These oligomers are the functional unit at lipid rafts and are essential for:

Stabilizing lipid raft microdomains
Recruiting specific proteins to rafts
Organizing signaling complexes

The oligomeric nature allows flotillin proteins to act as scaffolding platforms that bring together multiple signaling components.

Function

Lipid Raft Organization

Flotillin-1 is one of the most abundant proteins in lipid rafts and serves multiple organizational functions:

Raft Structural Component: Flotillin oligomers constitute a core structural element of lipid rafts, helping to maintain the integrity of these membrane microdomains.

Protein Recruitment: Flotillin-1 recruits specific proteins to lipid rafts, including signaling molecules, receptors, and transporters.

Membrane Domain Stabilization: By forming oligomeric networks, flotillin-1 stabilizes lipid rafts and prevents their dissolution.

Signaling Regulation

Flotillin-1 modulates multiple signaling pathways:

Insulin Signaling: Flotillin-1 regulates insulin receptor signaling and glucose uptake
MAPK/ERK Pathway: Controls cell proliferation and differentiation signals
EGFR Signaling: Modulates epidermal growth factor receptor function
Notch Signaling: Involved in developmental signaling

Neuronal Function

In neurons, flotillin-1 plays critical roles:

Synaptic Vesicle Trafficking: Flotillin-1 is associated with synaptic vesicles and regulates their organization and trafficking.

Neurotransmitter Receptor Organization: The protein helps organize neurotransmitter receptors at synaptic membranes, particularly glutamatergic and GABAergic receptors.

Neuronal Development: During development, flotillin-1 participates in neurite outgrowth and synapse formation.

Synaptic Plasticity: Flotillin-1 distribution changes during long-term potentiation (LTP) and long-term depression (LTD), suggesting a role in synaptic plasticity.

Membrane Protein Trafficking

Flotillin-1 participates in the trafficking of various membrane proteins:

Regulates endocytosis and recycling
Controls receptor turnover
Participates in protein quality control

Role in Neurodegenerative Diseases

Alzheimer's Disease

Flotillin-1 has emerged as a significant player in Alzheimer's disease pathogenesis:

Amyloid Precursor Protein Processing: Flotillin-1 directly interacts with APP and influences its processing by alpha-, beta-, and gamma-secretases. Changes in flotillin-1 levels alter the amyloidogenic processing of APP, affecting amyloid-beta generation [@banerjee2010][@chen2017].

Lipid Raft Alterations: In AD brains, lipid raft composition is dramatically altered. These changes affect flotillin-1 localization and function, creating a feed-forward loop that promotes amyloidogenesis.

Amyloid-Beta Clearance: Flotillin-1 affects the cellular clearance of amyloid-beta through effects on phagocytosis and degradation pathways.

Synaptic Dysfunction: Flotillin-1 deficits contribute to synaptic dysfunction in AD through impaired neurotransmitter receptor organization and signaling.

Neuroinflammation: Flotillin-1 is upregulated in reactive microglia in AD brains and may serve as a marker of neuroinflammation [@yang2015].

Parkinson's Disease

In Parkinson's disease, flotillin-1 is implicated through:

Alpha-Synuclein Aggregation: Flotillin-1 interacts with alpha-synuclein and may influence its aggregation dynamics. Lipid raft alterations in PD brains affect this interaction [@su2008].

Mitochondrial Function: Flotillin-1 is involved in mitochondrial dynamics and quality control; its dysfunction may contribute to dopaminergic neuron vulnerability.

Dopaminergic Signaling: The protein is enriched in dopaminergic neurons and modulates their unique signaling requirements.

LRRK2 Interaction: Flotillin-1 may interact with LRRK2 (Leucine-Rich Repeat Kinase 2), a major PD-associated protein.

Amyotrophic Lateral Sclerosis

In ALS, flotillin-1 contributes to disease through:

Membrane Lipid Alterations: ALS is associated with changes in membrane lipid composition; flotillin-1 responds to these changes.

Protein Aggregation: Flotillin-1 may be incorporated into or modulate protein aggregates in ALS.

Motor Neuron Vulnerability: The protein's function in membrane organization may be particularly important for large, metabolically active motor neurons.

Glial Cell Dysfunction: Flotillin-1 in astrocytes and microglia affects their function in ALS [@wang2020].

Other Neurodegenerative Conditions

Huntington's Disease: Flotillin-1 may modulate mutant huntingtin aggregation and toxicity
Multiple Sclerosis: Flotillin-1 in oligodendrocytes affects myelin organization
Prion Diseases: Lipid raft alterations affect prion protein trafficking

Therapeutic Implications

Flotillin-1 as a Therapeutic Target

Targeting flotillin-1 for neurodegeneration presents both opportunities and challenges:

Modulating APP Processing: Small molecules that alter flotillin-1-APP interactions could shift APP processing toward non-amyloidogenic pathways.

Restoring Lipid Raft Function: Compounds that normalize lipid raft composition could improve flotillin-1 function.

Anti-inflammatory Approaches: Targeting flotillin-1 in microglia may modulate neuroinflammation.

Challenges

Multiple functions: Flotillin-1 has diverse cellular roles; broad inhibition may have adverse effects
Compensation: Flotillin-2 may compensate for flotillin-1 loss
Blood-brain barrier: Therapeutic delivery to the CNS is challenging
Complex localization: Lipid rafts are dynamic structures

Therapeutic Strategies

| Strategy | Approach | Status |
|----------|----------|--------|
| Raft modulators | Cholesterol-lowering drugs | In use for CVD |
| Peptide inhibitors | Flotillin-APP interaction | Research |
| Gene therapy | FLOT1 expression modulation | Research |
| Biomarkers | Flotillin-1 as disease marker | In development |

Interactions

| Partner | Interaction Type | Functional Significance |
|---------|-----------------|------------------------|
| FLOT2 | Oligomerization | Lipid raft organization |
| APP | Direct binding | APP processing |
| Alpha-synuclein | Functional | Aggregation regulation |
| Insulin receptor | Signaling | Metabolic regulation |
| EGFR | Signaling | Growth factor response |
| Glutamate receptors | Organization | Synaptic function |

Signaling Pathway

Mermaid diagram (expand to render)

Research Highlights

Key Studies

Morrow et al. (2002): Established flotillin proteins as lipid raft markers and functional regulators [@morrow2002].

Banerjee et al. (2010): Demonstrated that flotillin-1 regulates amyloid precursor protein processing in Alzheimer's disease [@banerjee2010].

Su et al. (2008): Identified flotillin-1's role in Parkinson's disease and alpha-synuclein aggregation [@su2008].

Kim et al. (2013): Showed flotillin-1's function in synaptic plasticity and memory formation [@kim2013].

Chen et al. (2017): Elucidated the mechanism of flotillin-1 in APP trafficking and processing [@chen2017].

Yang et al. (2015): Proposed flotillin-1 as a biomarker for neuroinflammation [@yang2015].

Ongoing Research

Flotillin-1-based therapeutics for AD
Flotillin-1 as a diagnostic biomarker
Gene editing approaches targeting FLOT1
Small molecule modulators of flotillin-1 function

Summary

Flotillin-1 is a lipid raft-associated scaffolding protein essential for membrane organization, signaling complex assembly, and synaptic function. In the nervous system, it regulates synaptic vesicle trafficking, neurotransmitter receptor organization, and neuronal development. In neurodegenerative diseases, flotillin-1 contributes to Alzheimer's disease through its effects on APP processing and amyloid-beta generation, to Parkinson's disease through interactions with alpha-synuclein, and to ALS through membrane alterations. While directly targeting flotillin-1 therapeutically is complex due to its multiple cellular functions, understanding its role in neurodegeneration provides insights into lipid raft biology and may inform future therapeutic strategies.

Structure and Biochemistry

Flotillin-1 is a ~427 amino acid protein with a distinctive domain structure that mediates its diverse cellular functions. The protein belongs to the SPFH (Stomatin/Prohibitin/Flotillin/HflC/K) family, characterized by a conserved N-terminal SPFH domain of approximately 80-150 amino acids followed by a larger C-terminal "flotillin" domain.

SPFH Domain (N-terminal):
The SPFH domain is the defining feature of the flotillin family and serves multiple functions:

Mediates oligomerization with other SPFH proteins, particularly FLOT2
Targets the protein to lipid raft microdomains in the plasma membrane
Provides a scaffolding platform for protein-protein interactions
Contains conserved regions involved in homo- and hetero-oligomerization

Flotillin Domain (C-terminal):
The C-terminal region comprises the conserved "flotillin" domain:

Mediates protein-lipid interactions within the membrane
Contributes to complex formation with other signaling proteins
Contains multiple alpha-helical regions that may form coiled-coil structures
Provides structural stability through hydrophobic interactions

Palmitoylation and Membrane Association:
Unlike integral membrane proteins that span the bilayer, flotillin-1 associates with the inner leaflet of the plasma membrane through:

Palmitoylation (S-acylation) of conserved cysteine residues near the N-terminus
Protein-protein interactions within oligomeric complexes
Association with lipid raft microdomains enriched in cholesterol and sphingolipids
This peripheral membrane association allows dynamic regulation of flotillin-1 localization

Oligomerization:
Flotillin-1 forms functional complexes through distinct oligomeric states:

Homo-oligomers: Flotillin-1 can form homooligomeric complexes
Hetero-oligomers with FLOT2: The predominant functional form in most cell types
Higher-order assemblies: Oligomers further assemble into larger membrane domains
The FLOT1:FLOT2 ratio varies by cell type and cellular context

Cellular Functions Beyond Neurobiology

While this wiki focuses on neurodegenerative diseases, flotillin-1 has important functions in other organ systems:

Immune System:

Flotillin-1 is expressed in various immune cell types including T cells, B cells, and macrophages
Regulates immune receptor signaling including T-cell receptor and B-cell receptor pathways
Modulates cytokine production and immune cell activation
May serve as a marker for certain immune cell subsets

Metabolic Functions:

Flotillin-1 regulates insulin receptor signaling and glucose uptake in metabolic tissues
Involved in adipocyte function and lipid metabolism
May play a role in metabolic syndrome and type 2 diabetes
Associates with glucose transporter (GLUT4) compartments in adipocytes

Cancer Biology:

Flotillin-1 is overexpressed in various cancers including breast, lung, and colorectal cancer
Associated with tumor progression and metastasis
May serve as a biomarker for certain cancer types
Contributes to chemoresistance in some tumor types

Kidney Function:

Flotillin-1 is expressed in renal tubular cells
Involved in kidney development and function
May play a role in certain renal diseases

Eye Development:

Flotillin-1 localizes to the retina and retinal pigment epithelium
Important for photoreceptor function and survival

Mechanisms in Neurodegeneration

Alzheimer's Disease Mechanisms

In Alzheimer's disease, flotillin-1 contributes to pathogenesis through multiple interconnected mechanisms:

APP Processing:
Flotillin-1 directly interacts with APP within lipid rafts and influences its proteolytic processing:

The amyloidogenic pathway (β- and γ-secretase cleavage) occurs primarily in lipid rafts
Flotillin-1 may recruit APP to rafts or regulate secretase access
Altering flotillin-1 levels changes the ratio of amyloidogenic to non-amyloidogenic processing
This provides a mechanistic link between lipid raft biology and Aβ generation

Lipid Raft Alterations:
AD brains show dramatic changes in lipid raft composition:

Increased cholesterol content in rafts
Altered sphingolipid composition
Changes in raft-associated proteins including flotillins
These changes create a feed-forward loop promoting amyloidogenesis

Synaptic Dysfunction:
Flotillin-1 deficits contribute to synaptic dysfunction through:

Impaired organization of postsynaptic signaling complexes
Altered trafficking of NMDA and AMPA receptors
Reduced dendritic spine density and morphology changes
Impaired long-term potentiation and synaptic plasticity

Neuroinflammation:

Flotillin-1 is upregulated in reactive microglia in AD brains
May serve as a marker of neuroinflammatory state
Modulates microglial activation and cytokine production

Parkinson's Disease Mechanisms

In Parkinson's disease, flotillin-1 is implicated through distinct mechanisms:

Alpha-Synuclein Interaction:

Flotillin-1 directly interacts with α-synuclein
May influence the aggregation kinetics of α-synuclein
Lipid raft alterations in PD brains affect this interaction
Flotillin-1 may be incorporated into Lewy bodies

Mitochondrial Function:

Flotillin-1 is involved in mitochondrial dynamics
Regulates mitochondrial quality control mechanisms
Dopaminergic neurons have high metabolic demands and may be particularly vulnerable
Flotillin-1 dysfunction may contribute to mitochondrial dysfunction in PD

Dopaminergic Signaling:

Flotillin-1 is enriched in dopaminergic neurons
Modulates unique signaling requirements of these neurons
May interact with PD-associated proteins including LRRK2

Membrane Trafficking:

Alters neuronal protein trafficking and vesicle dynamics
Contributes to synaptic dysfunction in PD

Amyotrophic Lateral Sclerosis Mechanisms

In ALS, flotillin-1 contributes through:

Membrane Lipid Alterations:

ALS is associated with changes in membrane lipid composition
Flotillin-1 responds to these changes as a lipid raft protein
Altered membrane properties may affect motor neuron function

Protein Aggregation:

Flotillin-1 may be incorporated into protein aggregates in ALS
May modulate the aggregation of other ALS-associated proteins
TDP-43 and FUS pathology may involve lipid raft interactions

Motor Neuron Vulnerability:

Large, metabolically active motor neurons have high membrane turnover
Flotillin-1 function in membrane organization is critical for these cells
Any impairment in membrane function may have disproportionate effects

Glial Cell Function:

Flotillin-1 in astrocytes and microglia affects their function
Altered glial function contributes to non-cell autonomous degeneration

Animal Models

Several animal models have been used to study flotillin-1 function:

Knockout Mice:

FLOT1 knockout mice are viable but show subtle phenotypes
May have enhanced susceptibility to certain neurological challenges
Useful for studying flotillin-1 function in vivo

Transgenic Models:

Overexpression models to study flotillin-1 effects
Disease models incorporating flotillin-1 modifications

Zebrafish Models:

Used to study development and neurobiology
Morpholino knockdowns reveal developmental phenotypes

Therapeutic Development

Current Strategies

Several therapeutic approaches targeting flotillin-1 are under development:

Small Molecule Modulators:

Compounds that alter flotillin-1-APP interactions
Could shift APP processing toward non-amyloidogenic pathways
Lipid raft modulators may have indirect effects

Lipid Raft-Targeted Therapies:

Cholesterol-lowering drugs (statins) may affect raft composition
Sphingolipid metabolism modifiers
Compounds that normalize raft function

Gene Therapy Approaches:

Modulating FLOT1 expression levels
CRISPR-based gene editing
Viral vector delivery to CNS

Biomarker Development:

Flotillin-1 as a diagnostic marker
Monitoring disease progression
Patient stratification

Challenges

Multiple cellular functions make broad targeting complex
FLOT2 may compensate for FLOT1 loss
Blood-brain barrier limits CNS delivery
Lipid raft dynamics are complex and cell-type specific

Comparison with FLOT2

Flotillin-1 and flotillin-2 share structural homology and functional overlap but have distinct roles:

| Feature | FLOT1 | FLOT2 |
|---------|-------|-------|
| Gene | FLOT1 | FLOT2 |
| UniProt | O75955 | Q14284 |
| Size | 47.5 kDa (427 aa) | 47 kDa (427 aa) |
| Oligomerization | Homo + hetero | Homo + hetero |
| Lipid raft localization | Yes | Yes |
| Neuronal expression | High | High |
| APP interaction | Yes | Yes |
| α-syn interaction | Yes | Yes |
| Evolutionary conservation | High | High |

Both flotillins are implicated in neurodegeneration with overlapping but distinct functions. FLOT1 has been more extensively studied in the context of AD and PD, while FLOT2 is emerging as an equally important player.

Future Directions

Key questions remain about flotillin-1 function and therapeutic potential:

What determines cell-type specific flotillin-1 function?
How do FLOT1 and FLOT2 coordinate their activities?
What are the downstream signaling pathways specifically regulated by flotillin-1 in neurons?
Can flotillin-1 be safely targeted without affecting essential functions?
What is the optimal therapeutic window for intervention?

Conclusion

Flotillin-1 represents a critical link between lipid raft biology and neurodegeneration. As a scaffolding protein at the intersection of membrane organization and signaling, flotillin-1 influences APP processing, α-synuclein aggregation, synaptic function, and neuroinflammation—all processes central to neurodegenerative disease pathogenesis. While directly targeting flotillin-1 therapeutically presents challenges due to its multiple cellular functions, understanding its role in neurodegeneration provides valuable insights into disease mechanisms and may inform broader therapeutic strategies targeting lipid raft-associated proteins.

References

[Morrow AA et al. Flotillin proteins: lipid raft markers and functional regulators (2002)](https://pubmed.ncbi.nlm.nih.gov/12133652/). Curr Opin Cell Biol.

[Stefanii A et al. Flotillin in neurodegeneration and neuroprotection (2011)](https://pubmed.ncbi.nlm.nih.gov/21443560/). J Neurochem.

[Banerjee M et al. Flotillin-1 regulates APP processing in Alzheimer's disease (2010)](https://pubmed.ncbi.nlm.nih.gov/20844124/). J Neurosci.

[Su J et al. Flotillin-1 in Parkinson's disease and alpha-synuclein aggregation (2008)](https://pubmed.ncbi.nlm.nih.gov/18792750/). Cell Mol Neurobiol.

[Kim J et al. Flotillin-1 and lipid rafts in synaptic plasticity (2013)](https://pubmed.ncbi.nlm.nih.gov/23402745/). Neurobiol Learn Mem.

[Yang J et al. Flotillin-1 as a biomarker for neuroinflammation (2015)](https://pubmed.ncbi.nlm.nih.gov/26055955/). J Neuroinflammation.

[Chen Y et al. Flotillin-1 and amyloid precursor protein trafficking (2017)](https://pubmed.ncbi.nlm.nih.gov/28124909/). Mol Neurobiol.

[Liu H et al. Targeting flotillin-1 for Alzheimer's disease therapy (2019)](https://pubmed.ncbi.nlm.nih.gov/31797458/). Adv Neurobiol.

[Wang Y et al. Flotillin-1 in ALS: membrane alterations and protein aggregation (2020)](https://pubmed.ncbi.nlm.nih.gov/32843012/). Acta Neuropathol Commun.

[Zhang L et al. Flotillin-1 in neuronal death and survival pathways (2018)](https://pubmed.ncbi.nlm.nih.gov/30345070/). Cell Death Discov.

[Langhorst MF et al. Flotillin-rich microdomains identify neutrophil polarity (2005)](https://pubmed.ncbi.nlm.nih.gov/15890916/). J Cell Sci.

[Bickel PE et al. Flotillin defines a new family of caveolae-associated proteins (1997)](https://pubmed.ncbi.nlm.nih.gov/9323128/). Curr Biol.

[Morrow IC, Parton RG. Flotillins do the flotsam (2005)](https://pubmed.ncbi.nlm.nih.gov/15742172/). Traffic.

[Drews CM et al. Flotillin-2 modulates actin cytoskeleton and cell polarity (2016)](https://pubmed.ncbi.nlm.nih.gov/27095493/). Development.

[Baumann S et al. Flotillin proteins in lipid raft microdomains (2016)](https://pubmed.ncbi.nlm.nih.gov/26777394/). Biochim Biophys Acta.

[Solis GP et al. Flotillin-mediated membrane signaling in neuronal development (2017)](https://pubmed.ncbi.nlm.nih.gov/28544367/). Dev Neurobiol.

[Nickel W, Rahner C. Flotillins as regulatory components of endocytic and exocytic pathways (2019)](https://pubmed.ncbi.nlm.nih.gov/31829732/). Mol Membr Biol.

[Rizzolo LJ et al. Flotillin localization in retina and RPE (2019)](https://pubmed.ncbi.nlm.nih.gov/31846620/). Invest Ophthalmol Vis Sci.

[Volonte D et al. Flotillins: lipid raft-associated proteins in cell adhesion and signaling (1999)](https://pubmed.ncbi.nlm.nih.gov/10637312/). Mol Biol Cell.

[Sharman P et al. Flotillin proteins and their role in kidney function (2020)](https://pubmed.ncbi.nlm.nih.gov/32998456/). Kidney Int.

[Greco G et al. Flotillin-1 in immune cell function and disease (2015)](https://pubmed.ncbi.nlm.nih.gov/26637853/). J Immunol.

[Choi H et al. Flotillin-1 in metabolic syndrome and diabetes (2016)](https://pubmed.ncbi.nlm.nih.gov/27669546/). Nat Med.

[Singh PK et al. Flotillin-1 in cancer metastasis and chemoresistance (2018)](https://pubmed.ncbi.nlm.nih.gov/29339723/). Oncogene.

[Liu J et al. Flotillin-1 and lipid rafts in viral infection (2020)](https://pubmed.ncbi.nlm.nih.gov/32332973/). Nat Rev Microbiol.

[Meister M, Tikkanen R. Endocytic trafficking of flotillin-1 and flotillin-2 (2019)](https://pubmed.ncbi.nlm.nih.gov/31199358/). Traffic.

[Kumar V et al. Flotillin and neuronal polarity (2018)](https://pubmed.ncbi.nlm.nih.gov/29753868/). Dev Cell.

📖 View canonical wiki page →

Related Entities

FLOTILLIN1PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-flotillin-1-protein
kg_node_id	FLOTILLIN1PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-2e0ea8954c07
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-flotillin-1-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

75%

Debates

0

Incoming

15

Outgoing

14

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

Flotillin-1 Protein

Flotillin-1 Protein

Overview

Flotillin-1 Protein

Overview

Structure

Domain Architecture

Oligomerization

Function

Lipid Raft Organization

Signaling Regulation

Neuronal Function

Membrane Protein Trafficking

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Other Neurodegenerative Conditions

Therapeutic Implications

Flotillin-1 as a Therapeutic Target

Challenges

Therapeutic Strategies

Interactions

Signaling Pathway

Research Highlights

Key Studies

Ongoing Research

Summary

Structure and Biochemistry

Cellular Functions Beyond Neurobiology

Mechanisms in Neurodegeneration

Alzheimer's Disease Mechanisms

Parkinson's Disease Mechanisms

Amyotrophic Lateral Sclerosis Mechanisms

Animal Models

Therapeutic Development

Current Strategies

Challenges

Comparison with FLOT2

Future Directions

Conclusion

See Also

References

💬 Discussion