gene

ACSL4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about ACSL4: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

761Connections

4Hypotheses

3Analyses

50Outgoing

50Incoming

Summary

ACSL4 is a gene implicated in neurodegeneration research. Key relationships include: inhibits, regulates, activates. Associated with ALS, Als, Alzheimer. Connected to 288 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	ACSL4
Full Name	Acyl-CoA Synthetase Long Chain Family Member 4
Chromosome	Xq22.3
Protein Type	Synthetase
Target Class	Enzyme
Function	is an important component in the neurobiology of neurodegenerative diseases.
Mechanism of Action	Enzyme inhibition — blocking ACSL4 prevents incorporation of PUFAs into membrane phospholipids, reducing ferroptosis susceptibility
Primary Expression	various neural cell types:
Druggability	Low (0.41)
Clinical Stage	Phase III
Pathways	Autophagy, Cholesterol, Epigenetic, Ferroptosis, Inflammasome
UniProt ID	[O60488](https://www.uniprot.org/uniprot/O60488)
Ensembl ID	ENSG00000068366
GeneCards	ACSL4
Human Protein Atlas	ACSL4
Associated Diseases	ALS, Alzheimer's Disease, CANCER, Carcinoma, Fibrosis, Hepatocellular Carcinoma
Known Drugs/Compounds	ROSIGLITAZONE, CURCUMIN, Calycosin, curcumin, PIOGLITAZONE, valproic acid
Interactions	ALOX12, GPX4, MTOR, TNF, BAX, SCD1
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	ACSL4-Driven Ferroptotic Priming in Disease-Associ 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferro ACSL4-Ferroptotic Priming in Stressed Oligodendroc (+1 more)
KG Connections	760 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    ACSL4["ACSL4"] -->|"activates"| FERROPTOSIS["FERROPTOSIS"]
    ACSL4["ACSL4"] -->|"activates"| LIPID_PEROXIDATION["LIPID_PEROXIDATION"]
    ACSL4["ACSL4"] -->|"associated"| MS["MS"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Als["Als"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Carcinoma["Carcinoma"]
    ACSL4["ACSL4"] -->|"therapeutic target"| Autoimmune["Autoimmune"]
    TMEM16F["TMEM16F"] -->|"regulates"| ACSL4["ACSL4"]
    MIR130B3P["MIR130B3P"] -.->|"inhibits"| ACSL4["ACSL4"]
    SLC7A11["SLC7A11"] -->|"therapeutic target"| ACSL4["ACSL4"]
    MYC["MYC"] -->|"regulates"| ACSL4["ACSL4"]
    style ACSL4 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (561)

Target	Relation	Type	Str
FERROPTOSIS	activates	phenotype	1.00
Ferroptosis	mediates	process	0.95
PHOSPHATIDYLETHANOLAMINE	acylates	lipid	0.90
ARACHIDONIC_ACID	activates	lipid	0.90
GPX4	co_mentioned_with	gene	0.90
Ferroptosis	involved_in	process	0.90
Ferroptosis	contributes_to	process	0.90
FERROPTOSIS	promotes	process	0.90
oxidative stress response	participates_in	pathway	0.90
Fibrosis	contributes_to	disease	0.90
Ferroptosis	activates	pathway	0.90
GPX4	opposed_by	gene	0.85
ferroptosis	mediates	process	0.85
ferroptosis	participates_in	pathway	0.82
Alzheimer's Disease	associated_with	disease	0.82
LIPROXSTATIN-1	pathway_target_of	drug	0.80
SLC7A11	co_mentioned_with	gene	0.80
ferroptosis	promotes	process	0.80
MICROGLIA	upregulated_in	cell_type	0.80
Ferroptosis	promotes	process	0.80
ROSIGLITAZONE	inhibited_by	drug	0.75
Tumor	inhibits	disease	0.75
Neurodegeneration	activates	disease	0.75
Multiple Sclerosis	associated_with	disease	0.75
LIPID_PEROXIDATION	activates	phenotype	0.72
GPX4	inhibits	gene	0.70
MYC	regulates	gene	0.70
TNF	inhibits	gene	0.70
GSDMD	inhibits	gene	0.70
GPX4	regulates	gene	0.70
Ferroptosis	inhibits	pathway	0.70
Pyroptosis	inhibits	pathway	0.70
GENES	activates	gene	0.70
Apoptosis	activates	pathway	0.70
MS	associated_with	disease	0.70
FERROPTOSIS	inhibits	gene	0.70
Glycolysis	activates	pathway	0.70
PYROPTOSIS	inhibits	gene	0.70
unfolded protein response	participates_in	pathway	0.70
autophagy pathway	participates_in	pathway	0.70
MICROGLIA	protects_against	cell_type	0.70
MICROGLIA	activates	cell_type	0.70
MICROGLIA	regulates	cell_type	0.70
DEMENTIA	interacts_with	disease	0.70
DIABETES	inhibits	disease	0.70
ROSIGLITAZONE	inhibits	drug	0.65
Als	therapeutic_target	disease	0.65
Carcinoma	therapeutic_target	disease	0.65
Autoimmune	therapeutic_target	disease	0.65
Ms	therapeutic_target	disease	0.65

Incoming (200)

Source	Relation	Type	Str
TMEM16F	regulates	gene	1.00
MIR130B	downregulates	gene	0.95
MIR130B	inhibits	gene	0.95
Calycosin	binds	compound	0.90
h-seaad-v4-26ba859b	targets_gene	hypothesis	0.90
h-var-f96e38ec20	targets_gene	hypothesis	0.90
h-var-261452bfb4	targets_gene	hypothesis	0.90
h-var-22c38d11cd	targets_gene	hypothesis	0.90
Liproxstatin-1	downregulates	drug	0.85
Montelukast	downregulates	drug	0.85
Cadmium	upregulates	compound	0.80
MIR130B3P	inhibits	gene	0.72
SLC7A11	regulates	gene	0.70
PIOGLITAZONE	inhibits	drug	0.70
MTOR	targets	gene	0.65
FERROPTOSIS	targets	phenotype	0.65
CURCUMIN	regulates	drug	0.65
MTOR SIGNALING	targets	pathway	0.65
LIPID PEROXIDATION	activates	phenotype	0.65
LIPID PEROXIDATION	regulates	phenotype	0.65
METFORMIN	treats	drug	0.65
METFORMIN	activates	drug	0.65
SLC7A11	therapeutic_target	gene	0.60
MYC	regulates	gene	0.60
FASN	inhibits	gene	0.60
BAX	inhibits	gene	0.60
ALOX15	inhibits	gene	0.60
GSDMD	inhibits	gene	0.60
SCD1	inhibits	gene	0.60
HMGCR	inhibits	gene	0.60
TNF	inhibits	gene	0.60
MLKL	inhibits	gene	0.60
TFRC	activates	gene	0.60
SLC7A11	activates	gene	0.60
P38	activates	gene	0.60
GPX4	activates	gene	0.60
GPX4	associated_with	gene	0.60
PTGS2	expressed_in	gene	0.60
LOX	inhibits	gene	0.60
GOT1	activates	gene	0.60
HK2	activates	gene	0.60
ALOX5	activates	gene	0.60
GPX4	regulates	gene	0.60
GPX4/SLC7A11	regulates	gene	0.60
NRF2	regulates	gene	0.60
GPX4	inhibits	gene	0.60
ALOX12	inhibits	gene	0.60
MTOR	inhibits	gene	0.60
PRKAA1	associated_with	gene	0.60
SLC7A11	expressed_in	gene	0.60

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro	0.662	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri	0.515	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive	0.512	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo	0.493	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di

Mentioning Analyses (3)

Scientific analyses that reference this entity

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445]	Qin J, Ma S, Wang J, Huang S, Luan J, He	Cell death & disease	2026
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795]	Gao C, Liu B, Zhang R, Tian J, Xin H	Toxicology mechanisms and meth	2026
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890]	Rao W, Huang Y, Li J, Chen Q, Sun J et a	J Stroke Cerebrovasc Dis	2026
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892]	Lin D, Li K, Kuang W, Chen Z, Zhang M	World J Mens Health	2026
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496]	Che L, Zhu L, Zhou L, Zhou Y	Biochim Biophys Acta Rev Cance	2026
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570]	Chien Y, Xia R, Zhou D, Ai Y, Wu L et al	Hepatol Commun	2026
[The Chinese medicine Gandouling attenuates brain injury in hepatolenticular deg [PMID:41946579]	Wu K, Wang N, Zhao D, Wei W, Zhang W et	Zhejiang Da Xue Xue Bao Yi Xue	2026
Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease lin [PMID:41498558]	Singh P, Rath SL	Journal of Alzheimer's disease	2026
Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Media [PMID:41873334]	Song C, Wu X, Chen C, Shen B, He Y, Liu	Drug design, development and t	2026
Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent [PMID:41662914]	["Xin R", "Zhang J", "Zhang Y", "Dai M",	Free radical biology & medicin	2026
Acteoside alleviates sepsis-induced acute lung injury by activating the Nrf2 pat [PMID:41895086]	Wang Y, Zhang W, Zhang M, Zhu Y, Wang W,	Tissue & cell	2026
Ferroptosis and microglial polarization in retinal vein occlusion: pathological [PMID:41924362]	Xu J, Sun M, Wang C, Ju P, Guan XD, Xie	International journal of ophth	2026
Vitamin C inhibits ACSL4 to alleviate ferro-aging in primates. [PMID:41819088]	Liu L, Zheng Z, You W, Yang P, Wen Y et	Cell Metab	2026
Vitamin C slows primate aging by targeting iron-driven lipid peroxidation. [PMID:41950897]	Yu PL, Xu CR	Cell Metab	2026
The IL-33/ST2 Signaling Axis Alleviates Splenic Injury in Severe Acute Pancreati [PMID:41954769]	Cui L, Xu N, Chen J, Bin C, Feng Y et al	Pancreas	2026
Fibroblast-Specific GPX4 Deletion Exacerbates IBD via Lipid Peroxidation. [PMID:41955120]	Zhang Y, Ying Y, Huang W, Rosenfeld ZA,	Am J Physiol Gastrointest Live	2026
Melatonin Alleviates Erastin-Induced Cell Death by Inhibiting Ferroptosis and Am [PMID:40442550]	Wongjaikam S, Siengdee P, Somnus A, Govi	Neurotoxicity research	2025
Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in alzhei [PMID:40640358]	Zhu L, Zhou T, Wu L, Zhu X, Chen L, Zhan	Scientific reports	2025
Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathol [PMID:39510074]	["Zha Xu", "Liu Xicheng", "Wei Mengping"	Cell metabolism	2025
Upregulation of MAM by C99 disrupts ACSL4 activity and phospholipid homeostasis [PMID:41394684]	Montesinos J, Yun TD, Salomón-Cruz ID, A	bioRxiv : the preprint server	2025

ACSL4

Understanding Entity Pages

Summary

Wiki Pages (21)

ACSL4 Gene - Acyl-CoA Synthetase Long Chain Family Member 4

cbs-psp-daily-action-plan

Melatonin for Tauopathy: Comprehensive Evidence Synthesis

Ferroptosis in Alzheimer's Disease

Nanomedicine Approaches to Alzheimer's Disease

Ferroptosis in Neurodegeneration

Pathway Diagram

Outgoing (561)

Incoming (200)

Targeting Hypotheses (4)

Mentioning Analyses (3)

What determines the GPX4/ACSL4 balance that switches microglia from protective t

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

Related Papers (20)

ACSL4

Understanding Entity Pages

Summary

Wiki Pages (21)

ACSL4 Gene - Acyl-CoA Synthetase Long Chain Family Member 4

cbs-psp-daily-action-plan

Melatonin for Tauopathy: Comprehensive Evidence Synthesis

Ferroptosis in Alzheimer's Disease

Nanomedicine Approaches to Alzheimer's Disease

Ferroptosis in Neurodegeneration

Calcium Signaling Dysregulation in Alzheimer's Disease

Ferroptotic Neurons

PSP Ferroptosis and Iron-Dependent Cell Death

Ferroptosis

Ferroptosis in Alzheimer's Disease

alzheimers-disease

Autophagy Enhancement for Tauopathy

RAN Gene

Ferroptosis Pathway in Neurodegeneration

Oxidative Stress Pathway

Ferroptosis Pathway in Alzheimer's Disease

Ferroptosis Pathway in Neurodegeneration

Iron Dysregulation in Neurodegeneration

Oligodendrocyte-Myelin Dysfunction Hypothesis in Parkinson's Disease

Ferroptosis and Lipid Peroxidation in 4R-Tauopathies

Pathway Diagram

Outgoing (561)

Incoming (200)

Targeting Hypotheses (4)

Mentioning Analyses (3)

What determines the GPX4/ACSL4 balance that switches microglia from protective t

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

Related Papers (20)