FASLG - Fas Ligand

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FASLG - Fas Ligand

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FASLG - Fas Ligand

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FASLG - Fas Ligand</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>FASLG</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>FASLG - Fas Ligand</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=FASLG" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>

Pathway Diagram

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FASLG - Fas Ligand

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FASLG - Fas Ligand</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>FASLG</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>FASLG - Fas Ligand</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=FASLG" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

FASLG (Fas Cell Surface Death Receptor Ligand) is a gene encoding the Fas ligand (FasL/CD95L), a Type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. FasL is a critical effector of [apoptosis](/entities/apoptosis) (programmed cell death) and plays a significant role in immune privilege, tumor immune evasion, and neuronal cell death in neurodegenerative diseases. [@ethell2002]

Gene Information

Gene Symbol: FASLG
Official Name: Fas ligand (TNF superfamily, member 6)
Chromosomal Location: 1q24.3
NCBI Gene ID: 3564
Uniprot ID: P48023

Protein Structure and Function

The Fas ligand protein is a Type II transmembrane protein with the following structural features: [@mattson2000]

N-terminal intracellular domain: Contains a proline-rich region important for protein-protein interactions
Transmembrane domain: Anchors the protein to the cell membrane
C-terminal extracellular domain: The functional domain that binds to Fas receptors

FasL functions as a trimer and triggers apoptosis by binding to its cognate receptor Fas (CD95), forming the Fas-FasL death-inducing signaling complex (DISC). This activation leads to the recruitment of adaptor proteins (FADD) and initiator caspases (caspase-8), ultimately activating executioner caspases (caspase-3, -6, -7) that cleave cellular substrates and lead to cell death. [@combs2001]

Alternative Functions

Beyond apoptosis, FasL signaling can also: [@rohn2001]

Induce [necroptosis](/entities/necroptosis) (programmed necrosis) under certain conditions
Trigger inflammatory responses through [NF-κB](/entities/nf-kb) activation
Promote IL-1β release from glial cells
Modulate synaptic plasticity and neuronal excitability

Expression Patterns

FasL is expressed in various tissues with notable patterns relevant to neurodegeneration: [@yang2006]

Brain: Expressed in [neurons](/entities/neurons), [astrocytes](/entities/astrocytes), and [microglia](/cell-types/microglia-neuroinflammation)
Immune system: High expression in activated T lymphocytes and natural killer (NK) cells
Testis: High expression in Sertoli cells (immune privileged site)
Eye: Expressed in corneal and retinal cells (immune privileged sites)

In the brain, both neurons and glial cells can express FasL, creating a system for regulated cell death and immune modulation. [@jellinger2003]

Role in Neurodegenerative Diseases

Alzheimer's Disease

In [Alzheimer's disease](/diseases/alzheimers-disease) (AD), FasL plays a complex role in [amyloid-beta](/proteins/amyloid-beta) (Aβ)-induced neurotoxicity: [@wang2006]

Aβ-mediated FasL upregulation: Amyloid-beta peptides upregulate FasL expression in neurons and astrocytes, creating a pro-apoptotic environment [1]
Synaptic dysfunction: FasL signaling contributes to synaptic loss through caspase activation [2]
Microglial activation: Aβ can induce FasL expression in microglia, promoting neuroinflammation [3]
[Tau](/proteins/tau) pathology: FasL-mediated apoptosis may accelerate [tau](/proteins/tau) phosphorylation and spread [4]

Parkinson's Disease

In [Parkinson's disease](/diseases/parkinsons-disease) (PD), FasL is implicated in dopaminergic neuron loss: [@liu2010]

Mitochondrial dysfunction: Environmental toxins (e.g., MPTP, rotenone) upregulate FasL and trigger dopaminergic neuron apoptosis [5]
[α-Synuclein](/proteins/alpha-synuclein) aggregation: FasL expression is elevated in PD brains and may be induced by α-synuclein oligomers [6]
Microglial neurotoxicity: Activated microglia express FasL and can kill neurons through Fas-FasL interactions [7]
Genetic associations: Certain FASLG polymorphisms may increase PD risk [8]

Amyotrophic Lateral Sclerosis (ALS)

FasL contributes to motor neuron degeneration in ALS: [@guegan2003]

SOD1 mutations: Mutant SOD1 proteins upregulate FasL in motor neurons and astrocytes [9]
Non-cell autonomous toxicity: FasL expression in astrocytes mediates motor neuron death [10]
[TDP-43](/mechanisms/tdp-43-proteinopathy) pathology: TDP-43 aggregates are associated with increased FasL expression [11]

Other Neurodegenerative Disorders

Huntington's disease: FasL-mediated apoptosis contributes to striatal neuron loss [12]
Multiple sclerosis: FasL on autoreactive T cells and microglia contributes to demyelination [13]
Prion diseases: Prion protein aggregation induces FasL expression [14]

Therapeutic Implications

Targeting the Fas-FasL pathway represents a therapeutic strategy for neurodegenerative diseases: [@nagai2007]

FasL Inhibitors

Fas/Fc decoy receptors: Soluble Fas-Fc can block FasL signaling
Small molecule inhibitors: Various compounds are being developed to block DISC formation
Neutralizing antibodies: Anti-FasL antibodies can prevent apoptosis

Challenges

Immune suppression risk: Blocking FasL globally can increase cancer risk and autoimmune reactions
[Blood-brain barrier](/entities/blood-brain-barrier): Therapeutic agents must penetrate the BBB
Timing: Inhibiting apoptosis may be most effective in early disease stages

Current Research

Nanoparticle-delivered FasL inhibitors
Gene therapy approaches using AAV vectors
Combination therapies with other neuroprotective agents

Genetics

Polymorphisms

-844T>C polymorphism: Associated with altered FasL expression levels
-672A>G polymorphism: May influence autoimmune disease risk

Disease Associations

Certain FASLG variants have been linked to increased risk of:
Sporadic Parkinson's disease
Multiple sclerosis
ALS with autoimmune features

Interacting Proteins

FasL interacts with several proteins relevant to neurodegeneration: [@pasinelli2006]

FAS (CD95): Primary receptor mediating apoptosis
FADD: Adaptor protein in death receptor signaling
Caspase-8: Initiator caspase in extrinsic apoptosis
Caspase-3: Executioner caspase
DR5: Can also bind FasL in some contexts
X-linked inhibitor of apoptosis (XIAP): Regulated by FasL signaling

Diagnostic and Prognostic Potential

Biomarkers

Soluble FasL (sFasL) in cerebrospinal fluid (CSF) as a potential biomarker
Peripheral blood FasL levels correlate with disease progression in some studies

Research Applications

FasL expression as a marker for neuroinflammation
Tracking apoptosis in animal models of neurodegeneration

Additional evidence sources: [@trettel2000] [@sabelko1999] [@schultz2004]

External Links

[NCBI Gene: FASLG](https://www.ncbi.nlm.nih.gov/gene/3564)
[Uniprot: FASLG](https://www.uniprot.org/uniprotkb/P48023)
[OMIM: FASLG](https://www.omim.org/entry/134638)

References

[Ethell et al., Amyloid-beta-induced FasL upregulation (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/11862280/)

[Unknown, Mattson, Synaptic apoptosis in Alzheimer's disease (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/10774721/)

[Combs et al., Microglial FasL in Aβ toxicity (2001) (2001)](https://pubmed.ncbi.nlm.nih.gov/11292687/)

[Rohn et al., Caspase activation in tau pathology (2001) (2001)](https://pubmed.ncbi.nlm.nih.gov/11595185/)

[Yang et al., MPTP-induced FasL in dopaminergic neurons (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16629778/)

[Unknown, Jellinger, Alpha-synuclein and cell death in PD (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14569015/)

[Wang et al., Microglial FasL-mediated neurotoxicity (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16439995/)

[Liu et al., FASLG polymorphisms and PD risk (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20628659/)

[Guegan et al., SOD1 and FasL in ALS (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/14637012/)

[Nagai et al., Astrocyte-mediated motor neuron death (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17329282/)

[Pasinelli et al., TDP-43 in ALS (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/17023659/)

[Trettel et al., FasL in Huntington's disease (2000) (2000)](https://pubmed.ncbi.nlm.nih.gov/11094147/)

[Sabelko et al., FasL in multiple sclerosis (1999) (1999)](https://pubmed.ncbi.nlm.nih.gov/10408856/)

[Schultz et al., Prion protein and apoptosis (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15512880/)

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Related Entities

FASLG

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kg_node_id	FASLG
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-44771d64626b
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-faslg'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

297

Outgoing

310

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

FASLG - Fas Ligand

FASLG - Fas Ligand

Overview

Pathway Diagram

FASLG - Fas Ligand

Overview

Pathway Diagram

Gene Information

Protein Structure and Function

Alternative Functions

Expression Patterns

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Other Neurodegenerative Disorders

Therapeutic Implications

FasL Inhibitors

Challenges

Current Research

Genetics

Polymorphisms

Disease Associations

Interacting Proteins

Diagnostic and Prognostic Potential

Biomarkers

Research Applications

See Also

External Links

References

💬 Discussion