Affinage

ACSL5

Long-chain-fatty-acid--CoA ligase 5 · UniProt Q9ULC5

Length
683 aa
Mass
76.0 kDa
Annotated
2026-06-09
37 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACSL5 is a long-chain acyl-CoA synthetase that activates C16–C18 fatty acids—with a preference for unsaturated species—to acyl-CoA thioesters, channeling fatty acids toward beta-oxidation rather than triglyceride synthesis (PMID:9722683, PMID:17761945). Localizing predominantly to mitochondria, its activity is rate-limiting for hepatic fatty acid oxidation: overexpression suppresses diet-induced fatty liver while depletion exacerbates it (PMID:29605434, PMID:36208627). In the intestine ACSL5 governs long-chain fatty acid absorption and whole-body energy balance, and its loss limits food intake by raising distal intestinal fatty acid content and potentiating GLP-1/PYY secretion (PMID:26977393, PMID:38499083). ACSL5 protein levels and activity are tuned post-translationally—stabilized by USP29- and OTUB1-mediated deubiquitination (PMID:39355870, PMID:40280245) and activated by SIRT6-dependent deacetylation that licenses fatty acid oxidation and protects against fatty liver disease (PMID:36208627)—and its transcription is driven by oncostatin M via ERK, IRF-1/interferon-gamma, STAT3, p53, and ONECUT2, while being repressed by a JAB1/CRL4B complex (PMID:17761945, PMID:40546938, PMID:39557186, PMID:41355704, PMID:32129880, PMID:41388188). Through its control of fatty acid flux ACSL5 acts as a metabolic node in disease contexts, promoting apoptosis and lipoapoptosis (PMID:22163040, PMID:39557186), shaping ferroptosis sensitivity downstream of NPM1/SP1 (PMID:39927464), enhancing MHC-I antigen presentation and tumor immunity (PMID:38350448), and driving acetyl-CoA-dependent 53BP1 acetylation that engages p53-p21 senescence signaling (PMID:40595416). Regulatory variation at the ACSL5 locus, including a TCF7L2-region cis-regulatory element and the rs2419621 isoform-determining allele, links ACSL5 expression to fatty acid oxidation phenotypes and metabolic traits (PMID:27539148, PMID:29605434).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Established the core biochemical identity of ACSL5 as a long-chain acyl-CoA synthetase and defined its substrate preference, answering what reaction the enzyme catalyzes.

    Evidence Recombinant rat enzyme purified from E. coli and assayed in vitro against fatty acid substrates

    PMID:9722683

    Open questions at the time
    • Substrate profiling done with rat ortholog in vitro; tissue-specific substrate selectivity not addressed
    • No structural basis for chain-length preference
  2. 2007 High

    Showed ACSL5 directs fatty acids into beta-oxidation rather than triglyceride synthesis and is transcriptionally induced by oncostatin M through ERK, connecting enzyme activity to a metabolic fate decision.

    Evidence Transcriptional activation, siRNA knockdown, overexpression and fatty acid oxidation assays in HepG2 cells and hamster liver

    PMID:17761945

    Open questions at the time
    • Direct ERK target on the ACSL5 promoter not mapped
    • Did not establish in vivo physiological consequence
  3. 2016 High

    Defined the in vivo physiological role of ACSL5 in intestinal fat absorption and whole-body energy metabolism, moving beyond cell-based oxidation readouts.

    Evidence Whole-body ACSL5 knockout mice with calorimetry, triglyceride absorption, insulin tolerance, and FGF21 measurements

    PMID:26977393

    Open questions at the time
    • Whole-body KO cannot resolve tissue-of-origin for each phenotype
    • Mechanism linking ACSL5 loss to FGF21 elevation unresolved
  4. 2016 High

    Identified genomic regulation of ACSL5 expression, showing a TCF7L2-region T2D-associated variant acts as a cis-regulatory element physically contacting the ACSL5 promoter.

    Evidence CRISPR deletion in HCT116 plus 4C and Capture-C chromatin conformation capture

    PMID:27539148

    Open questions at the time
    • Functional metabolic consequence of altered ACSL5 expression via this element not measured
    • Relationship to TCF7L2 protein function not separated
  5. 2018 Medium

    Linked an ACSL5 coding/isoform variant to mitochondrial localization and fatty acid oxidation capacity in human tissue, connecting genotype to functional respirometry.

    Evidence Isoform overexpression in myoblasts, 14C-palmitate oxidation, subcellular fractionation, and human biopsy respirometry

    PMID:29605434

    Open questions at the time
    • Single lab, moderate sample size
    • Mechanism by which the 683-aa isoform localizes preferentially to mitochondria not defined
  6. 2022 High

    Revealed post-translational activation of ACSL5 by SIRT6-mediated deacetylation as a saturated-fatty-acid-responsive switch controlling fatty acid oxidation and fatty liver disease.

    Evidence Co-IP, deacetylation assay, deacetylation-mimic rescue in Sirt6 liver-KO mice, and NASH patient/mouse tissue analysis

    PMID:36208627

    Open questions at the time
    • Acetylation site(s) on ACSL5 and their effect on catalysis not fully mapped
    • Coordination with deubiquitination control unknown
  7. 2024 Medium

    Established deubiquitination as a second post-translational control point, with USP29 stabilizing ACSL5 against proteasomal degradation to sustain hepatic fatty acid oxidation.

    Evidence Co-IP, K48-linked ubiquitination assay, USP29 gain/loss in mice and hepatocytes with ACSL5 rescue

    PMID:39355870

    Open questions at the time
    • E3 ligase opposing USP29 not identified
    • Single lab
  8. 2024 High

    Defined the cellular mechanism of ACSL5-dependent appetite control, showing intestinal ACSL5 loss limits food intake via distal fatty acid–driven GLP-1/PYY secretion.

    Evidence Intestine-specific inducible KO with GLP-1/PYY measurement and GLP-1 receptor antagonist epistasis

    PMID:38499083

    Open questions at the time
    • Sensing mechanism translating luminal fatty acids into enteroendocrine secretion not detailed
    • Contribution of PYY versus GLP-1 not fully separated
  9. 2024 Medium

    Connected ACSL5 fatty acid metabolism to tumor immunity by showing it regulates MHC-I antigen presentation and CD8+ T cell sensitivity, with elaidic acid as an activating substrate.

    Evidence CD8+ T cell cytotoxicity, in vivo tumor models, MHC-I analysis, and ACSL5 substrate screening with gain/loss-of-function

    PMID:38350448

    Open questions at the time
    • Molecular link between acyl-CoA flux and MHC-I expression not resolved
    • Single lab
  10. 2024 Medium

    Demonstrated context-dependent pro-death signaling, with STAT3-induced ACSL5 driving lipoapoptosis in tubular cells in diabetic kidney disease.

    Evidence ACSL5 gain/loss in BUMPT cells, lipid and FFA assays, STAT3 knockdown rescue, promoter activity, and HFD/STZ mouse model

    PMID:39557186

    Open questions at the time
    • Lipid species mediating apoptosis not pinpointed
    • Single lab
  11. 2025 Medium

    Expanded post-translational stabilization control by identifying OTUB1 as a second deubiquitinase sustaining ACSL5 and fatty acid oxidation in acute liver injury.

    Evidence MS substrate identification, Co-IP, ubiquitination assay, and OTUB1 gain/loss with FAO measurement

    PMID:40280245

    Open questions at the time
    • Relationship between OTUB1 and USP29 regulation of the same target unclear
    • Single lab
  12. 2025 Medium

    Placed ACSL5 within a ferroptosis/apoptosis-resistance axis downstream of NPM1/SP1 in rhabdomyosarcoma, linking it to AURKB-targeted therapy response.

    Evidence AURKB inhibition with NPM1/SP1/ACSL5 epistasis and apoptosis/ferroptosis assays in vitro and in vivo

    PMID:39927464

    Open questions at the time
    • How ACSL5 acyl-CoA products modulate ferroptosis lipid peroxidation not defined
    • Single lab
  13. 2025 Medium

    Uncovered a p53–ACSL5 feedback circuit reprogramming central metabolism under glutamine deprivation in colorectal cancer, coupling ACSL5 to oxaliplatin sensitivity.

    Evidence ACSL5 gain/loss, p53 ChIP, MDM2 stabilization, IDH2 and PGAM1 activity, ROS, and chemosensitivity assays

    PMID:41355704

    Open questions at the time
    • Direct biochemistry of ACSL5–MDM2/MIB1 competition not structurally resolved
    • Single lab
  14. 2025 Medium

    Linked ACSL5-driven fatty acid oxidation to nuclear signaling via acetyl-CoA-dependent 53BP1 acetylation engaging p53-p21 senescence, and identified DNMT1 silencing in bladder cancer.

    Evidence ACSL5 gain/loss, acetyl-CoA and 53BP1-K1360 acetylation assays, DNMT1 knockdown, and tumor models

    PMID:40595416

    Open questions at the time
    • Whether 53BP1 acetylation is a direct ACSL5-dependent event versus bulk acetyl-CoA effect not separated
    • Single lab
  15. 2025 Medium

    Added an interferon-gamma/IRF-1 transcriptional input and showed ACSL5 maintains ATP and reshapes the tubular cell lipidome by reducing ceramide and glycerolipid content.

    Evidence Multi-omics with IRF-1 perturbation and ACSL5 functional assays in kidney tubular cells and patient cohorts

    PMID:40546938

    Open questions at the time
    • Direct IRF-1 binding to the ACSL5 promoter not shown
    • Single lab
  16. 2025 Medium

    Identified transcriptional repression of ACSL5 by a JAB1/CRL4B complex co-occupying its promoter in breast cancer, adding a negative regulatory arm.

    Evidence ChIP co-occupancy, CUL4B stabilization, gene expression and proliferation/invasion assays

    PMID:41388188

    Open questions at the time
    • Mechanism by which CRL4B represses transcription at this locus unclear
    • Single lab
  17. 2026 Medium

    Showed ACSL5 enables metastatic adaptation to a palmitic acid–rich lung microenvironment through COX2/PGE2-EP4 activation of pro-survival signaling.

    Evidence ACSL5 gain/loss in breast cancer cells and mouse metastasis models, PGE2 measurement, signaling analysis, and 2-bromopalmitate treatment

    PMID:41570334

    Open questions at the time
    • Link between ACSL5 acyl-CoA products and COX2 induction not mechanistically resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple post-translational (acetylation, K48 deubiquitination) and transcriptional inputs are integrated to set ACSL5 activity in a given tissue, and whether ACSL5 acyl-CoA products signal directly versus through bulk metabolite pools, remain unresolved.
  • No structural model of ACSL5 catalysis or regulation
  • Opposing E3 ligase(s) for USP29/OTUB1 not identified
  • Mechanistic link from acyl-CoA flux to MHC-I, ferroptosis, and senescence outputs not directly established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 2 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-382551 Transport of small molecules 2
Partners
MDM2OTUB1SIRT6USP29

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Rat ACS5 (ACSL5) is a long-chain acyl-CoA synthetase that activates a wide range of saturated fatty acids (C16–C18 range) with preference for C16–C18 unsaturated fatty acids; the purified recombinant enzyme produced in E. coli demonstrated this substrate specificity directly. Recombinant protein overproduction in E. coli, purification to near-homogeneity, in vitro enzymatic activity assay with fatty acid substrates Journal of biochemistry High 9722683
2007 Oncostatin M (OM) transcriptionally activates ACSL5 (and ACSL3) in hepatic cells through the ERK signaling pathway, and overexpression of ACSL5 alone partitions fatty acids toward beta-oxidation rather than triglyceride synthesis; siRNA knockdown of ACSL5 abrogated the OM-induced enhancement of fatty acid oxidation. Transcriptional activation assay in HepG2 cells and hamster liver, siRNA knockdown, fatty acid oxidation assay, ACSL5 overexpression Arteriosclerosis, thrombosis, and vascular biology High 17761945
2016 ACSL5 knockout mice show ~80% reduction in ACSL activity in jejunal mucosa, reduced fat mass, increased energy expenditure, improved insulin sensitivity, elevated FGF21 (hepatic mRNA ~16-fold, serum ~13-fold), and delayed triglyceride absorption after olive oil gavage, establishing ACSL5 as a key regulator of intestinal fat absorption and whole-body energy metabolism. Whole-body ACSL5 knockout mouse model, ACSL enzyme activity assay, indirect calorimetry, olive oil gavage triglyceride absorption assay, insulin tolerance test, FGF21 measurement Molecular metabolism High 26977393
2018 The ACSL5 rs2419621 T allele is associated with higher levels of the 683-aa ACSL5 protein isoform (vs. the 739-aa isoform), which localizes predominantly to mitochondria and drives greater fatty acid oxidation; primary myotubes from T-allele carriers showed higher CO2 production from 14C-palmitic acid, and vastus lateralis biopsies showed higher mitochondrial complex I and II respiration. ACSL5 overexpression in C2C12 myoblasts, 14C-palmitic acid oxidation assay, subcellular localization by fractionation/Western blot, primary myotube respirometry, ex vivo mitochondrial high-resolution respirometry in human biopsies Metabolism: clinical and experimental Medium 29605434
2016 The genomic region harboring the T2D-associated SNP rs7903146 within TCF7L2 functions as a regulatory element that physically contacts the ACSL5 promoter; CRISPR-mediated deletion of this region reduces ACSL5 mRNA up to 30-fold and abolishes chromatin contacts with the ACSL5 promoter, identifying rs7903146 as a cis-regulatory variant controlling ACSL5 expression. CRISPR/Cas9 deletion in HCT116, global gene expression analysis, 4C and Capture-C chromatin conformation capture Diabetologia High 27539148
2022 Cytoplasmic SIRT6 deacetylates ACSL5 upon binding to saturated fatty acids (especially palmitic acid), which triggers SIRT6 nuclear export; deacetylation of ACSL5 by SIRT6 facilitates fatty acid oxidation and suppresses NAFLD. NASH tissues show reduced cytoplasmic SIRT6 and increased ACSL5 acetylation. Overexpression of a deacetylated ACSL5 mimic attenuated NAFLD in Sirt6 liver-specific KO mice. Co-IP, deacetylation assay (SIRT6-ACSL5 interaction), deacetylation-mimic overexpression in Sirt6 liver KO mice, fatty acid oxidation assay, hepatic ACSL5 OE and KD in vivo, patient/mouse NASH tissue analysis Molecular cell High 36208627
2022 Hepatic ACSL5 overexpression suppresses high-fat diet-induced NAFLD while ACSL5 depletion exacerbates it, demonstrating ACSL5 is a pro-fatty acid oxidation enzyme in liver whose activity is rate-limiting for NAFLD progression. Hepatic ACSL5 overexpression and shRNA knockdown in mice, HFD-induced NAFLD model, lipid accumulation and liver histology Molecular cell High 36208627
2014 ACSL5 overexpression in CaCo2 cells causes approximately 2-fold increase in mitochondrial mortalin (HSPA9), accompanied by disturbance of acyl-CoA/sphingolipid metabolism; this mitochondrial mortalin upregulation requires wild-type TP53 and is absent in cells with mutated TP53. Proteomics of isolated mitochondria from ACSL5 transfectants, tandem mass spectrometry lipid analysis, siRNA gene silencing, Western blotting, qRT-PCR in CaCo2, HEK293, Lovo, Colo320DM cells Cell and tissue research Medium 24770931
2011 siRNA-mediated silencing of ACSL5 in Jurkat T cells decreased PMA+Ionomycin-induced apoptosis to control levels and reduced mRNA expression of FAS, FASLG, and TNF, indicating ACSL5 promotes apoptosis in T lymphocytes. siRNA knockdown of ACSL5 in Jurkat T cells, flow cytometry apoptosis assay, qRT-PCR for apoptosis-related genes PloS one Medium 22163040
2024 USP29 interacts directly with ACSL5 and stabilizes it via K48-linked deubiquitination, preventing proteasomal degradation; the protective effect of USP29 on fatty acid beta-oxidation in MASLD is dependent on ACSL5. Co-IP, K48-linked ubiquitination assay, USP29 overexpression/deletion in mice and hepatocytes, ACSL5 rescue experiments, FAO gene expression Clinical and molecular hepatology Medium 39355870
2024 ACSL5 regulates MHC-I-mediated antigen presentation in tumor cells; elaidic acid (EA) is identified as a substrate/activator of ACSL5 that enhances MHC-I expression and sensitizes tumors to CD8+ T cell cytotoxicity and PD-1 blockade therapy. In vitro cytotoxicity assay with CD8+ T cells, in vivo tumor models, MHC-I expression analysis, ACSL5 substrate screening, ACSL5 overexpression/KD in tumor cells Cell metabolism Medium 38350448
2024 Intestine-specific ACSL5 knockout (ACSL5IKO) mice are protected from diet-induced obesity exclusively through reduced food intake; this is mechanistically driven by increased FA content in the distal small intestine that elevates postprandial GLP-1 and PYY secretion; GLP-1 receptor antagonism partially restored food intake in ACSL5IKO mice. Intestine-specific conditional KO (tamoxifen-inducible villin-Cre), metabolic phenotyping, GLP-1/PYY measurement after TAG challenge, GLP-1 receptor antagonist treatment, dietary fat absorption and fecal lipid excreion assays Molecular metabolism High 38499083
2024 ACSL5 promotes lipoapoptosis in proximal tubular epithelial cells in diabetic kidney disease; ACSL5 knockdown reduces lipid deposition and lipoapoptosis while overexpression exacerbates them. STAT3 transcriptionally activates the ACSL5 promoter under high-glucose/palmitic acid conditions. ACSL5 KD and OE in BUMPT cells, Oil Red O staining, FFA ELISA, Western blot, STAT3 KD with ACSL5 OE rescue, ACSL5 promoter activity assay, HFD/STZ mouse model Molecular and cellular endocrinology Medium 39557186
2025 OTUB1 deubiquitinase interacts with ACSL5 and promotes its deubiquitination and protein stability, thereby enhancing fatty acid oxidation in APAP-induced acute liver injury; the protective effect of OTUB1 overexpression on FAO requires ACSL5. Mass spectrometry identification of ACSL5 as OTUB1 substrate, Co-IP, ubiquitination assay, OTUB1 OE/KD in vivo and in vitro, FAO measurement Biochemical pharmacology Medium 40280245
2025 AURKB inhibition suppresses RMS cell growth by inducing apoptosis and ferroptosis through a NPM1/SP1/ACSL5 signaling axis; ACSL5 is downstream of NPM1 and SP1 in mediating ferroptosis and apoptosis resistance in rhabdomyosarcoma cells. AURKB inhibition in vitro and in vivo, epistasis analysis with NPM1/SP1/ACSL5 knockdown/overexpression, apoptosis and ferroptosis assays JCI insight Medium 39927464
2025 In colorectal cancer cells under glutamine deprivation, ACSL5 is upregulated by p53 transcriptionally and in turn competes with MIB1 to stabilize MDM2, suppressing p53 in a feedback loop; ACSL5 mitochondrial localization activates IDH2 to accelerate the TCA cycle, while also relieving p53-mediated inhibition of PGAM1 to drive glycolysis; these metabolic changes generate ROS and sensitize cells to oxaliplatin. ACSL5 OE/KD in colorectal cancer cells, p53 ChIP and transcriptional assay, MDM2 stabilization assay, PGAM1 functional assay, IDH2 activity assay, ROS measurement, oxaliplatin sensitivity assay Advanced science Medium 41355704
2025 ACSL5 promotes fatty acid oxidation in bladder cancer cells; by enhancing FAO, ACSL5 increases intracellular acetyl-CoA levels, which in turn acetylate 53BP1 at K1360, enhancing recruitment of the p53-p21 senescence signaling axis in the nucleus and driving cellular senescence. ACSL5 expression is silenced in bladder cancer by DNMT1-mediated CpG island methylation. ACSL5 OE/KD, acetyl-CoA measurement, 53BP1 acetylation assay (K1360), p53-p21 pathway analysis, DNMT1 knockdown, in vitro and in vivo tumor models Oncogene Medium 40595416
2025 IRF-1 signaling (downstream of interferon-gamma) induces ACSL5 expression in kidney tubular cells; ACSL5 maintains ATP production and cell viability and shapes the lipid composition of tubular cells by reducing ceramide accumulation and glycerolipid content. Transcriptomic, metabolomic, and lipidomic analysis of experimental models and patient cohorts, IRF-1 signaling perturbation, ACSL5 functional assays in kidney tubular cells iScience Medium 40546938
2025 In breast cancer, JAB1 forms a transcriptional repressor complex with CRL4B (Cullin 4B-Ring E3 ligase) that co-occupies the promoters of PPARG and ACSL5, leading to their transcriptional repression and consequent activation of fatty acid metabolism. ChIP showing JAB1/CRL4B co-occupancy of ACSL5 promoter, CUL4B stabilization assay, gene expression analysis, proliferation/invasion assays with JAB1 manipulation Cell death and differentiation Medium 41388188
2020 ONECUT2 (OC2) transcription factor directly activates ACSL5 expression in gastric cancer cells; ChIP-seq and RNA-seq analyses revealed OC2 binding to the ACSL5 locus, and stable OC2 transfection increased ACSL5 expression. Stable OC2 transfection in GC cells, ChIP-seq, RNA-seq, OC2 knockdown with shRNA, correlation of OC2 and ACSL5 mRNA levels in patient database International journal of cancer Medium 32129880
2016 A splice variant of ACSL5 lacking exon 20 (ACSL5-Δ20) is causally linked to the migraine-associated SNP rs12355831; the functional variant rs2256368-G directly causes ~20–40% exon 20 skipping of ACSL5 mRNA, as shown by exon-skipping assay, implicating altered ACSL5 enzymatic activity (long-chain fatty acid activation) in mitochondria in migraine pathology. Exon-skipping assay, eQTL analysis in lymphoblastoid cell lines using GEUVADIS/1000 Genomes data European journal of human genetics Low 27189022
2023 ACSL5 knockdown reversed the anti-tumor effects of palmitic acid (C16:0) in A549 lung cancer cells (increased proliferation, apoptosis resistance, migration, invasion), and C16:0 treatment upregulated ACSL5 expression while inhibiting phosphorylated ERK, placing ACSL5 downstream of palmitic acid signaling in the ERK pathway. ACSL5 siRNA knockdown in A549 cells, C16:0 treatment, CCK-8, annexin V/PI apoptosis assay, wound healing/transwell assay, Western blot for pERK, mouse xenograft model European journal of histochemistry Low 37946526
2026 In lung-preferential metastatic breast cancer cells, ACSL5 mediates adaptation to the palmitic acid-enriched lung microenvironment by inducing COX2-mediated PGE2 accumulation, which activates PI3K/AKT and ERK signaling via EP4, promoting cancer cell survival and lung metastasis; ACSL5 also upregulates palmitoyltransferases to further enhance COX2 expression. ACSL5 gain/loss-of-function in breast cancer cell lines and mouse models, PGE2 measurement, signaling pathway analysis (PI3K/AKT, ERK), palmitoylation inhibitor (2-bromopalmitate) treatment, in vivo metastasis models Cancer research Medium 41570334
2025 SR-CR herbal components enhance ACSL5 activity via SIRT6-mediated deacetylation, promoting fatty acid oxidation; validated by surface plasmon resonance and molecular docking confirming constituent-protein interactions. Western blot, immunofluorescence, surface plasmon resonance, molecular docking, in vivo HFD rat model, HepG2 cell model Journal of ethnopharmacology Low 40254111

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes. Journal of biochemistry 130 9722683
2022 Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation. Molecular cell 86 36208627
2023 Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma. Oncogene 78 36932115
2016 Acyl CoA synthetase 5 (ACSL5) ablation in mice increases energy expenditure and insulin sensitivity and delays fat absorption. Molecular metabolism 77 26977393
2016 The type 2 diabetes presumed causal variant within TCF7L2 resides in an element that controls the expression of ACSL5. Diabetologia 62 27539148
2024 Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5. Cell metabolism 59 38350448
2020 A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis. Communications biology 54 32968195
2020 Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics. Cell reports 53 33113361
2007 Transcriptional activation of hepatic ACSL3 and ACSL5 by oncostatin m reduces hypertriglyceridemia through enhanced beta-oxidation. Arteriosclerosis, thrombosis, and vascular biology 53 17761945
2014 Casein kinase 1 regulates ethylene synthesis by phosphorylating and promoting the turnover of ACS5. Cell reports 46 25464840
2017 Acquired resistance to LY2874455 in FGFR2-amplified gastric cancer through an emergence of novel FGFR2-ACSL5 fusion. Oncotarget 44 28122360
2019 LOX and ACSL5 as potential relapse markers for pancreatic cancer patients. Cancer biology & therapy 36 30712446
2020 ONECUT2 upregulation is associated with CpG hypomethylation at promoter-proximal DNA in gastric cancer and triggers ACSL5. International journal of cancer 31 32129880
2024 The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers 25 38539505
2018 ACSL5 genotype influence on fatty acid metabolism: a cellular, tissue, and whole-body study. Metabolism: clinical and experimental 20 29605434
2011 High ACSL5 transcript levels associate with systemic lupus erythematosus and apoptosis in Jurkat T lymphocytes and peripheral blood cells. PloS one 16 22163040
2014 TP53 status regulates ACSL5-induced expression of mitochondrial mortalin in enterocytes and colorectal adenocarcinomas. Cell and tissue research 15 24770931
2024 USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination. Clinical and molecular hepatology 13 39355870
2016 A splice variant in the ACSL5 gene relates migraine with fatty acid activation in mitochondria. European journal of human genetics : EJHG 11 27189022
2024 Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity. Molecular metabolism 9 38499083
2014 Molecular cloning of the goose ACSL3 and ACSL5 coding domain sequences and their expression characteristics during goose fatty liver development. Molecular biology reports 9 24469710
2024 Structural characteristics of Lacticaseibacillus rhamnosus ACS5 exopolysaccharide in association with its antioxidant and antidiabetic activity in vitro. International journal of biological macromolecules 7 39357712
2024 ACSL5 promotes lipid deposition and lipoapoptosis in proximal tubular epithelial cells of diabetic kidney disease. Molecular and cellular endocrinology 7 39557186
2025 AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis. JCI insight 5 39927464
2020 A large deletion on CFA28 omitting ACSL5 gene is associated with intestinal lipid malabsorption in the Australian Kelpie dog breed. Scientific reports 5 33106515
2025 ACSL5 regulated acetyl-CoA to promote bladder cancer cellular senescence via 53BP1 acetylation. Oncogene 4 40595416
2018 Expression Analysis of ACSL5 and Wnt2B in Human Congenital Pulmonary Airway Malformations. The Journal of surgical research 4 30463708
2025 Scutellariae Radix and Coptidis Rhizoma improve NAFLD via regulation of SIRT6/ACSL5 pathway and SCD1. Journal of ethnopharmacology 3 40254111
2023 Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) <em>via</em> the ERK signaling pathway. European journal of histochemistry : EJH 3 37946526
2025 Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells. iScience 2 40546938
2025 ACSL5 mediates macrophage infiltration and lipid metabolism in erythrotelangiectasia rosacea via potential pathogenic mechanisms and therapeutic targets. Scientific reports 1 40195491
2025 OTUB1 enhances fatty acid oxidation in APAP-induced liver injury by mediating ACSL5 deubiquitination. Biochemical pharmacology 1 40280245
2025 JAB1/CRL4B complex represses PPARG/ACSL5 expression to promote breast tumorigenesis. Cell death and differentiation 1 41388188
2026 ACSL5 Mediates Adaptation to the Palmitic Acid-Enriched Pulmonary Microenvironment to Enhance Metastatic Breast Cancer Cell Survival and Lung Metastasis. Cancer research 0 41570334
2026 Novel homozygous variant in ACSL5 gene causing Congenital Diarrhea and Enteropathy (CODE) with sustained therapeutic success: a case report. BMC pediatrics 0 41572200
2025 ACSL5 Regulates Glucose Metabolism and Chemotherapy Sensitivity in Colorectal Cancer Cells under Glutamine Deficiency. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41355704
2025 Identification of a novel InDel locus within the ACSL5 gene and its association with body measurement traits in goats. Archives animal breeding 0 42256738

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