Affinage

ALDH1L1

Cytosolic 10-formyltetrahydrofolate dehydrogenase · UniProt O75891

Length
902 aa
Mass
98.8 kDa
Annotated
2026-06-09
48 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase) is a tetrameric enzyme central to folate one-carbon metabolism that consumes 10-formyltetrahydrofolate and thereby controls glycine biosynthesis, methylation flux, and de novo purine synthesis (PMID:35013550, PMID:36500483, PMID:37596270). Each identical subunit is a natural fusion of three functional domains: an N-terminal formyl-transfer domain, an intermediate acyl-carrier-protein domain bearing a covalently attached 4'-phosphopantetheine swinging arm, and a C-terminal NADP+-dependent aldehyde dehydrogenase domain; the swinging arm shuttles the formyl intermediate between protomers across the tetramer interface, making the tetrameric state obligatory for catalysis (PMID:35013550). In the C-terminal domain, Glu-673 restricts coenzyme affinity and Cys-707 senses coenzyme redox state by forming a transient covalent bond with the nicotinamide ring, allowing the enzyme to discriminate oxidized from reduced NADP (PMID:21540484, PMID:23295222). By depleting 10-formylTHF, ALDH1L1 expression elevates glycine while depleting serine, blocks the ZMP formylation step of purine synthesis, and reprograms downstream mitochondrial and methylation metabolism (PMID:36500483, PMID:37596270). ALDH1L1 also exerts non-metabolic regulatory functions: it inhibits cell motility through PP1/PP2A-mediated dephosphorylation of cofilin at Ser-3 to stabilize F-actin (PMID:20729910), and it drives a pro-apoptotic program in which JNK1/2 phosphorylate Bid at Thr59 to block its caspase-8 cleavage (PMID:25077544). Its abundance is tightly controlled: CHIP-mediated proteasomal degradation removes ALDH1L1 during S-phase to permit 10-formylTHF accumulation for purine synthesis (PMID:29979702), while in tumors and skeletal muscle the gene is epigenetically silenced by CpG-island promoter methylation and by DNMT3A promoter binding, respectively (PMID:21779486, PMID:33847380). Under oxidative stress, oxidatively modified ALDH1L1 binds HSP90β and translocates into mitochondria via TOM70, where it produces NADPH and protects TFAM from LONP1-mediated degradation (PMID:41184641).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2011 High

    Defining how the C-terminal ALDH domain handles its NADP coenzyme established the active-site logic of formyl oxidation, answering how the enzyme binds and discharges cofactor.

    Evidence Crystal structures of Glu-673 and Cys-707 point mutants with coenzyme binding assays

    PMID:21540484

    Open questions at the time
    • Did not resolve the full tetrameric architecture or inter-domain formyl transfer
    • Studied an isolated C-terminal domain rather than the intact enzyme
  2. 2013 High

    Capturing a covalent Cys-707-nicotinamide adduct explained the chemical basis by which the enzyme discriminates oxidized from reduced coenzyme.

    Evidence Crystal structures of C707S mutant with NADP+/NADPH and thio-NADP+ complexes

    PMID:23295222

    Open questions at the time
    • Catalytic relevance of the contracted conformation in the full-length tetramer not directly tested
  3. 2010 High

    Identifying ALDH1L1 as an inhibitor of cell motility via cofilin dephosphorylation revealed a non-metabolic cytoskeletal regulatory role distinct from its apoptotic function.

    Evidence FRAP, pyrene-actin assays, pharmacological PP1/PP2A inhibition, cofilin siRNA and phosphomutants in A549 cells

    PMID:20729910

    Open questions at the time
    • How ALDH1L1 connects mechanistically to PP1/PP2A activation is not defined
    • Whether the catalytic activity is required for cofilin effects beyond folate-dependence is unresolved
  4. 2014 High

    Linking ALDH1L1 to JNK1/2-mediated Bid Thr59 phosphorylation defined a pro-apoptotic signaling axis downstream of the enzyme.

    Evidence In vitro kinase assay, siRNA of JNK1/2 and Bid, Bid phosphomutants, fractionation in PC-3 cells

    PMID:25077544

    Open questions at the time
    • The signal connecting ALDH1L1 expression to JNK activation is not identified
    • Whether folate metabolism or the protein itself triggers JNK is unclear
  5. 2011 High

    Establishing CpG-island promoter methylation as the dominant mechanism silencing ALDH1L1 in cancers explained its frequent loss in tumors.

    Evidence Bisulfite sequencing of tumor/normal pairs, 5-aza-2'-deoxycytidine rescue, luciferase reporter

    PMID:21779486

    Open questions at the time
    • Does not identify the methyltransferase responsible in tumors
    • Functional consequence of restored expression on tumor phenotype not tested here
  6. 2018 Medium

    Showing CHIP-mediated proteasomal degradation of ALDH1L1 during S-phase explained how cells transiently relieve 10-formylTHF consumption for purine synthesis.

    Evidence Reciprocal co-IP, confocal co-localization, MG-132, CHIP siRNA/overexpression, thymidine block in NIH3T3 cells

    PMID:29979702

    Open questions at the time
    • Ubiquitination sites on ALDH1L1 not mapped
    • Single lab; cell-cycle dependence not validated in additional systems
  7. 2021 High

    Placing ALDH1L1 downstream of DNMT3A in skeletal muscle revealed an epigenetic repression circuit whose loss causes NADPH-driven ROS and mitochondrial dysfunction.

    Evidence Muscle-specific Dnmt3a KO mice, ALDH1L1 forced expression in myotubes, in vivo Aldh1l1 knockdown rescue, promoter chromatin binding, NADPH/ROS/respiration assays

    PMID:33847380

    Open questions at the time
    • Mechanistic link between ALDH1L1-driven NADPH and NADPH oxidase activation not fully detailed
    • Tissue specificity of this circuit outside muscle unknown
  8. 2022 High

    Cryo-EM of the intact tetramer resolved the obligate inter-protomer formyl transfer via the 4'-phosphopantetheine swinging arm, explaining why the tetramer is indispensable for catalysis.

    Evidence Cryo-EM structure determination of tetrameric rat ALDH1L1 with functional domain interaction analysis

    PMID:35013550

    Open questions at the time
    • Dynamics of arm movement during turnover not directly visualized
    • Structure is of rat enzyme; human-specific features inferred
  9. 2022 Medium

    Genetic loss-of-function metabolomics confirmed in living cells that ALDH1L1 controls glycine biosynthesis and methyl-group flux, validating its predicted metabolic role.

    Evidence shRNA and CRISPR knockout in RT4 bladder cancer cells with untargeted UHPLC-HR-MS metabolomics

    PMID:36500483

    Open questions at the time
    • Untargeted metabolomics does not establish direct flux through ALDH1L1
    • Single cell-line context
  10. 2023 Medium

    Gain-of-function metabolomics showed ALDH1L1 consumption of 10-formylTHF blocks the ZMP formylation step of purine synthesis, linking the enzyme to ZMP-dependent mitochondrial control.

    Evidence Metabolome analysis and mitochondrial activity assays in ALDH1L1-expressing HuH-7 cells

    PMID:37596270

    Open questions at the time
    • Causal mechanism of ZMP-mediated mitochondrial inhibition only partially defined
    • Single cell-line, single lab
  11. 2024 Medium

    Structural identification of an allosteric gossypol site on the C-terminal ALDH domain provided a pharmacological route to inhibit ALDH1L1 folate metabolism.

    Evidence Cryo-EM of human ALDH1L1 C-terminal domain with gossypol plus inhibition assay in NSCLC cells

    PMID:38917634

    Open questions at the time
    • Functional validation beyond structural observation is limited
    • Selectivity of gossypol for ALDH1L1 over related enzymes not established
  12. 2025 Medium

    Discovery of ROS-induced mitochondrial translocation via HSP90β/TOM70 revealed a moonlighting role in maintaining mitochondrial redox and TFAM stability.

    Evidence Co-IP/quantitative MS, fractionation, mitochondrial co-localization, HSP90β/TOM70 interaction, LONP1 degradation and knockout assays in cancer cells

    PMID:41184641

    Open questions at the time
    • The oxidative modification on ALDH1L1 required for HSP90β binding is not chemically defined
    • Generality across cell types not established
  13. 2025 Medium

    Identification of an ALDH1L1-STUB1-TOLLIP axis degrading viral N and E proteins extended ALDH1L1 function into autophagy-mediated antiviral restriction.

    Evidence Co-IP, knockdown/overexpression, autophagy inhibitor assays for porcine epidemic diarrhea virus

    PMID:41467838

    Open questions at the time
    • Direct vs. indirect nature of the complex interactions not fully resolved
    • Relevance to mammalian/human viruses untested
  14. 2025 Low

    A reported ALDH1L1-GLUL interaction driving glutamate accumulation and CD8+ T-cell exhaustion proposed a tumor-immune-microenvironment role.

    Evidence Co-IP, molecular docking, CD8+ T-cell transcriptomics, mitochondrial assays, in vivo mouse models

    PMID:41654886

    Open questions at the time
    • Single co-IP for GLUL interaction without reciprocal validation
    • Multi-step causal chain from interaction to T-cell exhaustion relies on inference
    • Whether enzymatic activity is required is unknown
  15. 2025 Medium

    Demonstrating in vitro retinaldehyde-to-retinoic-acid conversion and a requirement for ALDH1L1 in folic-acid rescue of neural tube defects proposed the enzyme as a metabolic bridge between folate and retinoic acid signaling.

    Evidence Xenopus pax3-knockdown NTD model, CRISPR/Cas9 aldh1l1 knockdown, in vitro enzymatic assay, retinaldehyde/RA rescue (preprint)

    PMID:bio_10.1101_2025.10.14.681787

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Physiological relevance of retinaldehyde oxidation versus its canonical formyl-THF activity in vivo unclear
    • Catalytic efficiency on retinaldehyde not benchmarked

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ALDH1L1's catalytic folate activity is mechanistically coupled to its diverse moonlighting roles (cytoskeletal, apoptotic, mitochondrial, antiviral, immunomodulatory) remains unresolved.
  • Whether enzymatic activity is required for each moonlighting function is mostly untested
  • Tissue- and context-specificity of these roles is not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 1 R-HSA-5357801 Programmed Cell Death 1
Partners
GLULHSP90B1STUB1TFAMTOLLIPTOMM70

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM structures of tetrameric rat ALDH1L1 revealed that it is a natural fusion of three unrelated domains: N-terminal domains remove formyl from 10-formyltetrahydrofolate, intermediate domains (homologs of acyl/peptidyl carrier proteins with covalently attached 4'-phosphopantetheine arm) transfer the formyl group between catalytic domains of different protomers, and C-terminal aldehyde dehydrogenase domains convert formyl to CO2. The tetrameric state is indispensable for catalysis because the intermediate domain transfers the formyl group between protomers across the tetramer interface. Cryo-EM structure determination of tetrameric rat ALDH1L1 Communications biology High 35013550
2011 Crystal structures of C-terminal domain (Ct-FDH) mutants showed that Glu-673 restricts coenzyme affinity (E673A causes irreversible NADP+ binding) and Cys-707 acts as a sensor of the coenzyme redox state (C707A mutant cannot differentiate between NADP+ and NADPH). These two conserved catalytic residues adjacent to the nicotinamide ring control binding and discharge of the NADP+ coenzyme. Crystal structures of Cys707 and Glu673 point mutants combined with coenzyme binding experiments The Journal of biological chemistry High 21540484
2013 Crystal structures of Ct-FDH with thio-NADP+ and of the C707S mutant with NADP+ and NADPH revealed that Cys-707 forms a covalent bond with the C4N atom of the nicotinamide ring during catalysis, trapping the coenzyme in a contracted conformation during the transition from oxidized to reduced form. This mechanism allows the enzyme to discriminate between oxidized and reduced coenzyme. Crystal structures of C707S mutant and thio-NADP+ complexes Chemico-biological interactions High 23295222
2017 Computational modeling using available domain structures showed that ALDH1L1 is a tetramer of identical subunits, each with three functional domains; the intermediate acyl carrier protein domain possesses a covalently attached 4'-phosphopantetheine prosthetic group that functions as a swinging arm to transfer the formyl reaction intermediate between the N-terminal and C-terminal catalytic domains. Models defined positions of the 4'-phosphopantetheine arm within both catalytic domains and predicted inter-domain interfaces. Computer modeling of domain interactions using available crystal structures Chemico-biological interactions Low 28414156
2010 ALDH1L1 (FDH) inhibits cell motility by stabilizing F-actin and promoting actin stress fibers through PP1- and PP2A-mediated dephosphorylation of cofilin at Ser-3. The PP1/PP2A inhibitor calyculin A prevented cofilin dephosphorylation and restored motility. This effect is independent of FDH-induced apoptosis (JNK inhibitor or pan-caspase inhibitor did not restore motility), is folate-dependent (increased folate prevented cofilin dephosphorylation), and is mediated through cofilin (siRNA knockdown of cofilin or expression of phosphorylation-deficient S3A mutant mimicked FDH effects, while S3D phosphomimetic mutant blocked them). FRAP of GFP-actin, pyrene-actin polymerization/depolymerization assays, pharmacological inhibitors, siRNA knockdown, cofilin phosphomutant expression in A549 cells Oncogene High 20729910
2014 In response to ALDH1L1 expression, JNK1 and JNK2 phosphorylate Bid at Thr59 within its caspase-8 cleavage site. Thr59 phosphorylation protects Bid from caspase-8 cleavage, causing accumulation of full-length Bid and its translocation to mitochondria. In vitro, all three JNK isoforms (JNK1-3) phosphorylated Thr59, with JNK1 being least active. siRNA silencing of JNK1/2 or Bid prevented Bid phosphorylation and accumulation, and rescued ALDH1L1-expressing cells from apoptosis. A T59D phosphomimetic mutant promoted cleavage of Bid to jBid. In vitro kinase assay, siRNA knockdown, expression of Bid phosphomutants, co-immunoprecipitation, subcellular fractionation in PC-3 prostate cancer cells Cell death & disease High 25077544
2018 ALDH1L1 is degraded during S-phase via proteasomal degradation mediated by the chaperone-dependent E3 ubiquitin ligase CHIP. CHIP co-localizes with ALDH1L1 and interacts with it (demonstrated by co-immunoprecipitation); siRNA silencing of CHIP halts ALDH1L1 loss, while transient CHIP overexpression promotes ALDH1L1 degradation. Proteasome inhibitor MG-132 prevents ALDH1L1 loss in proliferating cells. Downregulation of ALDH1L1 leads to accumulation of its substrate 10-formyltetrahydrofolate, required for de novo purine biosynthesis during S-phase. Co-immunoprecipitation, confocal microscopy co-localization, MG-132 proteasome inhibition, siRNA knockdown of CHIP, thymidine block cell-cycle arrest in NIH3T3 cells PloS one Medium 29979702
2011 ALDH1L1 promoter methylation is the major mechanism controlling FDH levels in human cancers. An extensive CpG island spanning -525 to +918 bp (96 CpG pairs, covering the promoter, exon 1, and part of intron 1) is extensively methylated (76-95% of CpGs) in cancer cell lines, while unmethylated in normal tissues. Treatment of FDH-deficient A549 cells with the methyltransferase inhibitor 5-aza-2'-deoxycytidine restored FDH expression. Exon 1 significantly increases ALDH1L1 transcriptional activity in a luciferase reporter assay. Bisulfite sequencing, 5-aza-2'-deoxycytidine treatment, luciferase reporter assay, patient tumor/normal tissue pairs Genes & cancer High 21779486
2021 DNMT3A suppresses ALDH1L1 transcription in skeletal muscle by binding to its promoter region and altering its epigenetic profile. Muscle-specific Dnmt3a knockout mice show elevated ALDH1L1 expression. Forced expression of ALDH1L1 elevates NADPH levels, which causes overproduction of ROS via the NADPH oxidase complex, resulting in mitochondrial dysfunction. In vivo knockdown of Aldh1l1 largely rescues exercise intolerance in Dnmt3a-deficient mice, placing ALDH1L1 downstream of DNMT3A in this pathway. Muscle-specific Dnmt3a knockout mice, ALDH1L1 forced expression in myotubes, in vivo Aldh1l1 shRNA knockdown, chromatin binding assay (DNMT3A binding to Aldh1l1 promoter), NADPH measurement, ROS measurement, mitochondrial respiration assay The EMBO journal High 33847380
2022 Loss of ALDH1L1 in RT4 bladder cancer cells (via shRNA or CRISPR knockout) leads to decreased glycine (8-fold) and decreased metabolites from S-adenosylmethionine-utilizing (methylation) pathways, establishing ALDH1L1 as a direct regulator of glycine biosynthesis and methyl group flux in living cells. Additional changes include decreased amino acids, Krebs cycle intermediates, and ribose-5-phosphate, and increased nicotinic acid. shRNA knockdown and CRISPR knockout of ALDH1L1 in RT4 cells, untargeted UHPLC-HR-MS metabolomics, supervised and unsupervised multivariate analysis Molecules (Basel, Switzerland) Medium 36500483
2023 ALDH1L1 expression in HuH-7 hepatocellular carcinoma cells consumes 10-formyltetrahydrofolate, causing ZMP (5-aminoimidazole-4-carboxamide ribonucleotide) accumulation by blocking the ZMP formylation step of de novo purine synthesis. This results in serine depletion and glycine increase intracellularly. The ZMP accumulation inhibits mitochondrial activity through a serine catabolism mechanism, and ALDH1L1-expressing cells show reduced ZMP sensitivity and higher mitochondrial activity. Metabolome analysis of ALDH1L1-expressing HuH-7 cells, intracellular metabolite measurement, mitochondrial activity assays Scientific reports Medium 37596270
2024 Gossypol binds to an allosteric site on the C-terminal aldehyde dehydrogenase domain of human ALDH1L1 and disrupts folate metabolism by preventing NADP+ binding, causing a shift in structural conformation to a closed-form NADP+-binding site. Cryo-EM structures of tetrameric C-terminal ALDH1L1 in complex with gossypol confirmed this allosteric inhibition mechanism. Cryo-EM structure of human ALDH1L1 C-terminal domain in complex with gossypol, ALDH1L1 inhibition activity assay in NSCLC cells Biochemical and biophysical research communications Medium 38917634
2025 Cytoplasmic ALDH1L1 translocates into mitochondria in a ROS-dependent feedback manner in cancer cells. ROS-mediated oxidative modification of ALDH1L1 is necessary for its interaction with HSP90β, which enables translocation into mitochondria via the TOM70 import channel. Once inside, mitochondrial ALDH1L1 produces NADPH to maintain mitochondrial redox homeostasis and binds TFAM to prevent its degradation by the protease LONP1. This was identified by co-immunoprecipitation followed by quantitative mass spectrometry. Co-immunoprecipitation followed by quantitative mass spectrometry, subcellular fractionation, co-localization with mitochondrial markers, HSP90β and TOM70 interaction assays, LONP1 degradation assay, ALDH1L1 knockout studies Cell death and differentiation Medium 41184641
2025 ALDH1L1 directly interacts with the E3 ubiquitin ligase STUB1 and the autophagy cargo receptor TOLLIP to mediate degradation of porcine epidemic diarrhea virus nucleocapsid (N) and envelope (E) proteins via the autophagosome-lysosomal pathway. This ALDH1L1-STUB1-TOLLIP axis constitutes a novel antiviral restriction mechanism. Co-immunoprecipitation, knockdown and overexpression experiments, autophagy pathway inhibitor assays Journal of virology Medium 41467838
2025 ALDH1L1 directly interacts with the glutamine synthetase enzyme GLUL (demonstrated by molecular docking and co-immunoprecipitation), leading to L-glutamate accumulation in the tumor microenvironment. This accumulated L-glutamate suppresses the PI3K/Akt/FoxO1 signaling axis in CD8+ T cells, impairing mitochondrial function and inhibiting oxidative phosphorylation, thereby driving CD8+ T-cell exhaustion. Co-immunoprecipitation, molecular docking, transcriptomic sequencing of CD8+ T cells, mitochondrial functional assays, in vivo mouse models Journal of translational medicine Low 41654886
2025 In a Xenopus pax3-knockdown model of folic acid-rescueable neural tube defects, ALDH1L1 (FTHFD) was shown to be required for folic acid protection: FA upregulates aldh1l1 expression, and CRISPR/Cas9 knockdown of ALDH1L1 abolishes the FA protective effect. Human ALDH1L1 enzyme was shown in vitro to convert retinaldehyde to retinoic acid (RA), establishing ALDH1L1 as an enzymatic bridge between folate metabolism and RA biosynthesis. Overexpression of ALDH1L1 restored neural tube closure in aldh1l1-knockdown embryos when retinaldehyde was provided. Xenopus pax3-knockdown NTD model, CRISPR/Cas9 knockdown of aldh1l1, in vitro enzymatic assay of human ALDH1L1 with retinaldehyde substrate, rescue experiments with RA/retinaldehyde and ALDH1L1 overexpression bioRxivpreprint Medium bio_10.1101_2025.10.14.681787

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Molecular comparison of GLT1+ and ALDH1L1+ astrocytes in vivo in astroglial reporter mice. Glia 211 21046559
2010 ALDH1L1 inhibits cell motility via dephosphorylation of cofilin by PP1 and PP2A. Oncogene 73 20729910
2007 The folate metabolic enzyme ALDH1L1 is restricted to the midline of the early CNS, suggesting a role in human neural tube defects. The Journal of comparative neurology 67 17111379
2016 Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice. F1000Research 63 28149504
2014 Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke. PLoS genetics 63 24651765
2013 Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia 58 23840004
2013 Aldh1L1 is expressed by postnatal neural stem cells in vivo. Glia 53 23836537
2018 ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer. Advances in experimental medicine and biology 51 30362096
2011 Epigenetic Silencing of ALDH1L1, a Metabolic Regulator of Cellular Proliferation, in Cancers. Genes & cancer 51 21779486
2019 Loss of ALDH1L1 folate enzyme confers a selective metabolic advantage for tumor progression. Chemico-biological interactions 42 30794800
2021 A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress. The EMBO journal 37 33847380
2011 Conserved catalytic residues of the ALDH1L1 aldehyde dehydrogenase domain control binding and discharging of the coenzyme. The Journal of biological chemistry 30 21540484
2014 The astrocyte marker Aldh1L1 does not reliably label enteric glial cells. Neuroscience letters 25 24589880
2014 JNK1/2 regulate Bid by direct phosphorylation at Thr59 in response to ALDH1L1. Cell death & disease 24 25077544
2018 CHIP E3 ligase mediates proteasomal degradation of the proliferation regulatory protein ALDH1L1 during the transition of NIH3T3 fibroblasts from G0/G1 to S-phase. PloS one 22 29979702
2021 Distribution of Aldh1L1-CreERT2 Recombination in Astrocytes Versus Neural Stem Cells in the Neurogenic Niches of the Adult Mouse Brain. Frontiers in neuroscience 21 34557065
2019 Astrocyte-specific transcriptome analysis using the ALDH1L1 bacTRAP mouse reveals novel biomarkers of astrogliosis in response to neurotoxicity. Journal of neurochemistry 20 31222732
2016 Transcriptional activity of novel ALDH1L1 promoters in the rat brain following AAV vector-mediated gene transfer. Molecular therapy. Methods & clinical development 18 27990448
2019 The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1. Frontiers in genetics 17 31737034
2021 Knockout of Putative Tumor Suppressor Aldh1l1 in Mice Reprograms Metabolism to Accelerate Growth of Tumors in a Diethylnitrosamine (DEN) Model of Liver Carcinogenesis. Cancers 16 34203215
2022 Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions. Molecules (Basel, Switzerland) 13 36500483
2023 One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression. Scientific reports 12 37596270
2022 Sex-Specific Metabolic Effects of Dietary Folate Withdrawal in Wild-Type and Aldh1l1 Knockout Mice. Metabolites 12 35629957
2020 The Combination of Loss of ALDH1L1 Function and Phenformin Treatment Decreases Tumor Growth in KRAS-Driven Lung Cancer. Cancers 12 32481524
2017 ALDH1L1 variant rs2276724 and mRNA expression predict post-operative clinical outcomes and are associated with TP53 expression in HBV-related hepatocellular carcinoma. Oncology reports 12 28714006
2018 Deep Sequencing Revealed a CpG Methylation Pattern Associated With ALDH1L1 Suppression in Breast Cancer. Frontiers in genetics 11 29868117
2015 Transcriptome profiling of sleeping, waking, and sleep deprived adult heterozygous Aldh1L1 - eGFP-L10a mice. Genomics data 11 26413480
2013 The mechanism of discrimination between oxidized and reduced coenzyme in the aldehyde dehydrogenase domain of Aldh1l1. Chemico-biological interactions 11 23295222
2022 Structure of putative tumor suppressor ALDH1L1. Communications biology 10 35013550
2021 Rab6A as a Pan-Astrocytic Marker in Mouse and Human Brain, and Comparison with Other Glial Markers (GFAP, GS, Aldh1L1, SOX9). Cells 9 33466322
2022 Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children. The American journal of clinical nutrition 8 35460232
2023 Ethanol-induced transcriptional and translational changes in Aldh1l1-Egfp/Rpl10a cortical astrocyte cultures. Frontiers in neuroscience 7 37415614
2025 Edaravone inhibits neuronal ferroptosis and alleviates acute Central nervous system injury induced by diquat via enhancement of METTL14-mediated m6A methylation of Aldh1l1. Free radical research 6 40130422
2017 Modeling of interactions between functional domains of ALDH1L1. Chemico-biological interactions 6 28414156
2016 Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 6 26993122
2023 Aldh1l1-Cre/ER is expressed in unintended cell types of the salivary gland, pancreas, and spleen. microPublication biology 5 37273576
2025 Aldh1l1-Cre/ERT2 Drives Flox-Mediated Recombination in Peripheral and CNS Infiltrating Immune Cells in Addition to Astrocytes During CNS Autoimmune Disease. Brain and behavior 3 39910805
2020 [Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer]. Molekuliarnaia biologiia 3 32392189
2025 Aldh1L1 Lineage Cells Contribute to the Functional Heterogeneity Within the Cells in Glial Scars After Spinal Cord Injury Through YAP Signaling. Glia 2 41090559
2024 Structural identification and comprehension of human ALDH1L1-Gossypol complex. Biochemical and biophysical research communications 1 38917634
2021 Reply to Krupenko et al. Comment on "Lee et al. The Combination of Loss of ALDH1L1 Function and Phenformin Treatment Decreases Tumor Growth in KRAS-Driven Lung Cancer Cancers 2020, 12, 1382". Cancers 1 34066916
2026 ALDH1L1 reverses CD8+ T cell exhaustion in the oral squamous cell carcinoma microenvironment by reprogramming L-glutamate metabolism. Journal of translational medicine 0 41654886
2026 The astrocyte marker ALDH1L1 also identifies a stromal cell population in the lymph node. Scientific reports 0 41663590
2025 Probing the metabolic regulator and candidate tumor suppressor ALDH1L1 as a target for non-small cell lung cancer gene therapy. Molecular therapy. Oncology 0 40984886
2025 Differential Expression of One-Carbon Pathway Enzyme ALDH1L1 Is Linked to Tumorigenicity of Low-Grade Bladder Cancer Cells Through Metabolic Reprogramming. Cancer medicine 0 41070972
2025 Mitochondria-transliterated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy. Cell death and differentiation 0 41184641
2025 ALDH1L1 suppresses the replication of porcine epidemic diarrhea virus by degrading viral nucleocapsid and envelope proteins. Journal of virology 0 41467838
2024 Untargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo. Metabolites 0 39728477

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