Affinage

GALC

Galactocerebrosidase · UniProt P54803

Length
685 aa
Mass
77.1 kDa
Annotated
2026-06-10
78 papers in source corpus 19 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALC is a lysosomal β-galactosidase that catalyzes the hydrolysis of galactolipids—including galactosylceramide (galactocerebroside) and galactosylsphingosine (psychosine)—removing their β-galactosyl headgroups from the ceramide backbone (PMID:7601472). To act on these amphipathic substrates, GALC partners with the saposin SapA, forming a heterotetramer in which an open channel connects the GALC active site to SapA's hydrophobic cavity, allowing a soluble hydrolase to access the buried glycosyl headgroup of membrane-embedded glycosphingolipids (PMID:29323104). Beyond galactosylceramide and psychosine, GALC deficiency drives accumulation of lactosylceramide, which itself acts as a neuroinflammatory metabolite (PMID:40305757). GALC is synthesized as a precursor that traffics to the lysosome and is proteolytically processed to its mature active form; disease-causing missense mutations frequently impair this lysosomal trafficking and maturation step, and residual GALC activity correlates tightly with mature lysosomal protein levels and with clinical severity by age of onset (PMID:26865610, PMID:23620143). Mis-trafficking is separable from secretion, and pharmacological chaperones such as NOEV can enhance precursor maturation of late-onset mutants (PMID:26108143). The enzyme is also secreted and taken up by neighboring cells in a partially M6P-receptor-dependent manner, enabling cross-correction in culture, though this transfer is inefficient in the peripheral nervous system in vivo (PMID:8812733, PMID:32375064, PMID:16732552). Loss of GALC function causes Krabbe disease (globoid cell leukodystrophy): GALC-deficient macrophages cannot degrade myelin-derived galactosylceramide and are transformed into globoid cells, while GALC enzymatic activity is required for primary myelination and, in heterozygotes, for microglial myelin debris clearance (via Trem2-dependent phagocytosis) and remyelination (PMID:32375064, PMID:23620143, PMID:28575206). Expression is constrained by a GC-rich, TATA-less promoter bearing Sp1 and YY1 elements together with inhibitory intronic sequences, and nonsense alleles are eliminated by nonsense-mediated mRNA decay (PMID:16759875, PMID:9441867).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Establishing that GALC encodes the enzyme hydrolyzing galactosylceramide and psychosine, and defining its genomic structure, anchored the gene as the catalytic basis for galactolipid turnover.

    Evidence Gene cloning, cDNA sequencing, genomic analysis, and enzyme activity assay

    PMID:7601472

    Open questions at the time
    • Did not resolve how a soluble hydrolase accesses membrane-embedded substrate
    • No cofactor requirement defined
  2. 1996 Medium

    Demonstrating secretion and uptake of active GALC by neighboring cells established cross-correction as a route for enzyme delivery and showed M6P-receptor uptake is only partly responsible.

    Evidence Retroviral transduction, [14C]-galactosylceramide metabolic labeling, lysosomal localization assay in fibroblasts

    PMID:8812733

    Open questions at the time
    • The non-M6P uptake route was not identified
    • In vivo relevance not addressed at this stage
  3. 1996 Medium

    Functional expression of a disease-associated mutant pinpointed a single residue critical for catalysis, beginning the structure-function mapping of GALC variants.

    Evidence COS-1 expression of the canine Y158S mutant with activity measurement

    PMID:8661004

    Open questions at the time
    • Single variant in a non-human ortholog
    • No structural rationale for the activity loss
  4. 1997 Medium

    Mapping the GALC promoter and inhibitory intronic elements explained the gene's constitutively low expression across cell types.

    Evidence CAT reporter assays with deletion constructs identifying Sp1/YY1 sites and inhibitory sequences

    PMID:9441867

    Open questions at the time
    • Trans-acting factor binding not validated in vivo
    • Tissue-specific regulation not resolved
  5. 1999 Medium

    A mini-gene assay proved an intronic mutation causes exon 6 skipping, extending disease mechanisms beyond coding changes to splicing defects.

    Evidence GALC mini-gene transfection with RT-PCR splicing analysis

    PMID:10464649

    Open questions at the time
    • Single mutation tested
    • Effect on protein/enzyme not directly measured
  6. 2006 High

    Identifying NMD-mediated decay of the twitcher nonsense allele explained the absence of GALC protein and defined a transcript-level disease mechanism.

    Evidence mRNA quantification and rescue with NMD inhibitors in twitcher Schwann cells

    PMID:16759875

    Open questions at the time
    • Therapeutic relevance of NMD inhibition not established
    • Restricted to one nonsense allele
  7. 2006 Medium

    Lentivirally expressed GALC accumulating in lysosomes and correcting deficient cells via conditioned medium confirmed the secretory cross-correction route in neural cells.

    Evidence Lentiviral transduction, immunofluorescence colocalization, activity rescue of twitcher glia

    PMID:16732552

    Open questions at the time
    • In vivo efficiency not tested here
    • Uptake receptor not defined
  8. 2013 High

    A knockin mutant with normal precursor but no activity dissociated catalytic loss from protein production and revealed a role for GALC in primary myelination (dysmyelination).

    Evidence GALCtwi-5J (E130K) mouse with activity, Western blot, neuropathology and EM

    PMID:23620143

    Open questions at the time
    • Molecular basis of dysmyelination vs demyelination not fully resolved
    • Single mutation
  9. 2016 High

    Showing that severe mutants and cis-polymorphisms specifically reduce lysosomal trafficking and processing established mis-trafficking as a determinant of phenotype and explained imperfect genotype-phenotype correlation.

    Evidence Subcellular fractionation with activity assays comparing whole-cell vs lysosomal GALC across mutants

    PMID:26865610

    Open questions at the time
    • Trafficking machinery interactions not mapped
    • Did not test in vivo CNS consequences
  10. 2015 Medium

    Demonstrating that NOEV chaperones mutant GALC and enhances precursor maturation provided a small-molecule strategy to rescue trafficking-defective late-onset variants.

    Evidence Activity, heat-stability, fibroblast treatment, maturation Western blot, and docking

    PMID:26108143

    Open questions at the time
    • In vivo efficacy not shown
    • Limited to a subset of late-onset mutants
  11. 2018 High

    The GALC–SapA heterotetramer structure resolved how a soluble hydrolase reaches membrane-buried glycosyl headgroups through a channel to the SapA hydrophobic cavity, defining the catalytic mechanism on lipid substrates.

    Evidence Cryo-EM/crystal structure of GALC-SapA complex with functional validation

    PMID:29323104

    Open questions at the time
    • Dynamics of substrate extraction not captured
    • Saposin specificity rules generalize beyond tested partner unverified
  12. 2017 High

    Heterozygous GALC mice exhibiting impaired remyelination, reduced microglial phagocytosis and Trem2 revealed a haploinsufficiency-linked role in myelin debris clearance.

    Evidence Cuprizone model in GALC+/- mice with phagocytosis, Trem2 readouts, and NKH-477 rescue

    PMID:28575206

    Open questions at the time
    • Mechanism linking GALC dosage to Trem2 unresolved
    • Human heterozygote relevance not tested
  13. 2020 High

    Macrophage-specific deletion and patient transplant data established a macrophage-autonomous mechanism driving globoid cell formation and showed cross-correction fails in vivo in the PNS.

    Evidence Novel GLD mouse model, macrophage-specific GALC deletion, psychosine measurement, patient HSCT histopathology

    PMID:32375064

    Open questions at the time
    • Molecular trigger of globoid transformation not fully defined
    • Why PNS cross-correction fails not mechanistically explained
  14. 2025 Medium

    A zebrafish galcb knockout that accumulates lactosylceramide rather than psychosine, with LacCer injection driving neuroinflammation, identified LacCer as a distinct neuroinflammatory metabolite of GALC deficiency.

    Evidence CRISPR zebrafish KO, lipidomics, intraventricular LacCer injection, immunohistochemistry

    PMID:40305757

    Open questions at the time
    • Relative contribution of LacCer vs psychosine in mammals unclear
    • Single model organism
  15. 2024 Medium

    A comprehensive variant panel quantitatively linked residual activity to mature lysosomal protein levels and to clinical severity, while showing mis-trafficking is separable from secretion.

    Evidence GALC-KO human oligodendrocytic cell line, expression/activity/secretion assays, psychosine MS (preprint)

    PMID:39464077

    Open questions at the time
    • Preprint, not peer-reviewed
    • Secretion-competent mis-trafficking variants mechanistically unexplained
  16. 2025 Medium

    Recombinant GALC enzyme replacement restored activity and autophagic markers at physiological dose but impaired them at supra-physiological dose, indicating dose-sensitive control of the lysosomal-autophagic pathway.

    Evidence Recombinant murine GALC enzyme replacement in KD primary cells with LC3/p62 immunoblot and viability assays

    PMID:40590240

    Open questions at the time
    • Mechanism of supra-physiological toxicity unknown
    • In vivo dosing window not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GALC dosage mechanistically couples to broader pathways implicated by emerging models (microglial Trem2 regulation, amyloid processing, autophagy homeostasis) and which lipid species dominate human neuropathology.
  • No mechanistic link between GALC and amyloid processing established
  • Causal lipid driver in human CNS not defined
  • Pathway connection of GALC to senescence/cancer findings non-physiological

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005764 lysosome 4 GO:0005576 extracellular region 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2 R-HSA-9612973 Autophagy 1
Partners
PSAP
Complex memberships
GALC-SapA heterotetramer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 GALC and the saposin SapA form a heterotetramer complex that creates an open channel connecting the GALC active site to the SapA hydrophobic cavity, revealing the mechanism by which a soluble lysosomal hydrolase cleaves the polar glycosyl headgroups of glycosphingolipids (galactocerebroside) from their hydrophobic ceramide tails. This structure also defines how specificity of saposin binding to hydrolases is encoded. Cryo-EM/crystal structure of GALC-SapA complex with functional validation Nature Communications High 29323104
1995 GALC catalyzes the lysosomal hydrolysis of galactolipids including galactosylceramide (galactocerebroside) and galactosylsphingosine (psychosine). The gene spans ~60 kb and consists of 17 exons, establishing the genomic organization relevant to understanding enzyme structure-function. Gene cloning, cDNA sequencing, genomic library analysis, enzyme activity assay Genomics High 7601472
1996 GALC is secreted into the media by transduced fibroblasts and taken up by untransduced neighboring cells. Mannose-6-phosphate receptor-mediated uptake is only partially responsible for the efficient transfer of GALC to neighboring cells (cross-correction). The transferred GALC is localized to lysosomes and is functionally active, as demonstrated by normal metabolism of [14C]stearic acid-labeled galactosylceramide. Retroviral transduction, GALC activity assay, [14C]-substrate metabolic labeling, lysosomal localization assay Biochemical and molecular medicine Medium 8812733
2020 Cross-correction of GALC does not occur efficiently in vivo in the peripheral nervous system. Galc-deficient Schwann cells autonomously produce psychosine. Galc-deficient macrophages cannot degrade myelin and are transformed into globoid cells upon exposure to galactosylceramide, producing a more severe GLD phenotype. Hematopoietic stem cell transplantation reduces globoid cells in patient nerves via phagocytic activity of healthy macrophages rather than cross-correction. Novel GLD mouse model, macrophage-specific GALC deletion, psychosine measurement, histopathology, hematopoietic stem cell transplantation in patients Neuron High 32375064
2016 Infantile-onset GALC mutants show reduced trafficking to lysosomes and reduced proteolytic processing compared to later-onset mutants when measured in the lysosomal fraction, even when total cell lysate activity appears similar. Cis-polymorphisms in GALC also affect lysosomal trafficking and processing, explaining imperfect genotype-phenotype correlations. Subcellular fractionation, GALC activity assay in lysosomal vs. whole-cell fractions, site-directed mutagenesis, cell transfection The Journal of Neuroscience High 26865610
1996 Expression studies in COS-1 cells demonstrated that the A to C transversion at cDNA position 473 (Y158S) is the disease-causing mutation in canine GLD, establishing this specific amino acid as critical for GALC enzymatic activity. COS-1 cell expression assay, site-directed mutagenesis, GALC activity measurement Genomics Medium 8661004
2006 The twitcher mouse has a premature stop codon (W339X) in GALC that triggers nonsense-mediated mRNA decay (NMD), resulting in reduced GALC transcript levels proportional to the number of twitcher alleles. NMD inhibitors (anisomycin, emetine, puromycin) restored GALC transcript levels in twitcher-derived Schwann cells, confirming NMD as the mechanism by which no GALC protein is detected. RT-PCR/Northern blot for mRNA quantification, NMD inhibitor treatment, immunocytochemistry, Western blot Neurobiology of Disease High 16759875
2006 GALC expressed from lentiviral vectors accumulates in lysosomes of transduced neural cells and is also secreted to the extracellular medium. Conditioned GALC-containing medium corrects GALC deficiency in non-transduced twitcher glial cultures, confirming the secretory pathway of lysosomal enzyme delivery. Lentiviral transduction, immunofluorescence for lysosomal colocalization, GALC activity assay in conditioned medium and non-transduced cells The journal of gene medicine Medium 16732552
1997 The 5' flanking region of the human GALC gene is GC-rich with no CAAT or TATA sequences, contains Sp1 and YY1 binding sites, and a construct spanning nucleotides -176 to -24 has the strongest promoter activity. Inhibitory sequences exist immediately upstream of the promoter and in the first 234 nt of intron 1, which together with a suboptimal nucleotide at +4 explain the low levels of GALC protein in all cell types. Chloramphenicol acetyltransferase reporter gene assay with deletion constructs, promoter activity measurement Biochemical and molecular medicine Medium 9441867
1997 An intronic mutation IVS6+5G>A in the GALC gene causes exon 6 skipping. Transfection of a GALC mini-gene harboring this mutation proved that this specific intronic change is the cause of exon 6 skipping, resulting in loss of function. GALC mini-gene transfection assay, RT-PCR analysis of splicing Genetic testing Medium 10464649
2007 The novel GALC p.Gly41Ser substitution abolishes catalytic activity of galactocerebrosidase, as demonstrated by expression studies, and is responsible for late-onset Krabbe disease in a Sicilian founder population. Expression studies (cell transfection), GALC enzymatic activity assay Human mutation Medium 17579360
2013 The GALCtwi-5J missense mutation (E130K) causes loss of enzymatic activity despite normal levels of precursor protein, indicating the mutation disrupts catalytic function rather than protein production. The PNS is severely hypomyelinated and lacks large diameter axons (dysmyelination rather than demyelination), supporting a role for GALC enzymatic activity in primary myelination. Mouse model characterization, GALC activity assay, Western blot for precursor protein, neuropathology, electron microscopy Human molecular genetics High 23620143
2017 Heterozygous GALC mutant mice (GALC+/-) have reduced myelin debris clearance and diminished remyelination after cuprizone-induced demyelination. The microglial phagocytic response and elevation of Trem2 (necessary for clearing damaged myelin) are markedly reduced in GALC+/- animals. These defects were corrected in vitro by NKH-477 treatment. Cuprizone demyelination model in GALC+/- mice, histological analysis of remyelination, microglial phagocytosis assay, Trem2 expression analysis, pharmacological rescue Human molecular genetics High 28575206
2015 N-octyl-4-epi-β-valienamine (NOEV) acts as a pharmacological chaperone for mutant GALC proteins: it inhibits GALC activity in cell lysates, stabilizes GALC activity under heat denaturation, and significantly increases enzyme activity of late-onset GALC mutants in COS1 cells and patient fibroblasts. NOEV enhances maturation of GALC precursor to its mature active form. Structural modeling showed NOEV binds to the active site. In vitro GALC activity assay with NOEV, heat denaturation stability assay, patient fibroblast treatment, GALC precursor maturation assay (Western blot), molecular docking Journal of human genetics Medium 26108143
2025 In a zebrafish model, galcb (but not galca) knockout dramatically decreases total GALC activity. Galcb KO zebrafish accumulate lactosylceramide (LacCer) rather than predominantly psychosine in the brain. Intraventricular injection of LacCer upregulates proinflammatory markers and increases macrophage infiltration, identifying LacCer as a potential neuroinflammatory metabolite in GALC deficiency. CRISPR/Cas9 zebrafish knockout, GALC activity assay, targeted lipidomic analysis, intraventricular LacCer injection, immunohistochemistry, gene expression analysis Brain Medium 40305757
2024 31 clinically-relevant GALC missense variant proteins were assessed: 26 reduced GALC activity by 92-100% vs. wild-type. Residual GALC activity strongly correlates with mature, lysosomal GALC protein levels (Pearson r=0.93). Many low-activity missense variants do not correspondingly impair GALC secretion, indicating mis-trafficking to lysosomes is a separable defect. GALC activity correlates with clinical disease severity based on age of onset (Pearson r=0.98 for homozygous missense). Psychosine levels were negatively correlated with GALC activity among pathogenic variants. CRISPR-Cas9 GALC-KO human oligodendrocytic cell line, transient expression assays, GALC activity assay, GALC secretion assay, psychosine quantification by mass spectrometry bioRxiv (preprint)preprint Medium 39464077
2020 GALC overexpression in fibroblasts induces cell cycle arrest and upregulation of p16, p21, and p53, with downregulation of hTERT, driving a senescent phenotype. Senescent GALC-overexpressing fibroblasts in co-culture significantly increase colorectal cancer cell proliferation and migration. GALC overexpression in fibroblasts, co-culture with CRC cells, cell cycle analysis, gene expression for p16/p21/p53/hTERT, proliferation and migration assays Frontiers in Oncology Low 32318333
2020 GALC knockout using CRISPR-Cas9 in neuronal cell models did not lead to alpha-synuclein accumulation, arguing against a direct causal relationship between GALC loss-of-function and alpha-synuclein aggregation. CRISPR-Cas9 GALC knockout, alpha-synuclein immunostaining/Western blot Brain Medium 36370000
2025 Heterozygous loss-of-function mutations in GALC have a gene-dosage effect on Aβ40 levels in brain interstitial fluid in C57BL/6 mice and significantly increase Aβ plaque formation in the 5xFAD mouse model of AD, placing GALC lysosomal activity in the pathway regulating amyloid processing. Heterozygous GALC mouse model, microdialysis for brain interstitial Aβ40, Aβ plaque quantification in 5xFAD/GALC+/- mice bioRxiv (preprint)preprint Low
2025 Recombinant murine GALC (rm-GALC) at physiological dose restores dose-dependent enzymatic activity in KD primary cells without adverse viability effects, and restores autophagic function (normalized LC3 and p62 markers). Supra-physiological GALC doses impair autophagy and decrease cell viability, indicating that precise dosing of GALC is required for lysosomal-autophagic pathway homeostasis. HEK293T-expressed recombinant GALC purification, in vitro enzyme replacement in KD primary cells, GALC activity assay, LC3/p62 immunoblotting, cell viability assay Advanced Biology Medium 40590240

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Two proliferative stages of the oligodendrocyte lineage (A2B5+O4- and O4+GalC-) under different mitogenic control. Neuron 254 2223090
1993 Glial cell mitogens bFGF and PDGF differentially regulate development of O4+GalC- oligodendrocyte progenitors. Developmental biology 157 8405684
1995 A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease. Human molecular genetics 99 7581365
2010 Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease. Human mutation 98 20886637
1995 Structure and organization of the human galactocerebrosidase (GALC) gene. Genomics 81 7601472
1995 Characterization of the large deletion in the GALC gene found in patients with Krabbe disease. Human molecular genetics 75 8634707
1996 Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers. Genomics 74 8661004
1995 Oligodendroblasts distinguished from O-2A glial progenitors by surface phenotype (O4+GalC-) and response to cytokines using signal transducer LIFR beta. Developmental biology 74 7875381
1997 Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene and identification of the mutation causing globoid cell leukodystrophy (Krabbe disease) in this primate. Genomics 60 9192853
2006 Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation. Journal of human genetics 58 16607461
2020 Macrophages Expressing GALC Improve Peripheral Krabbe Disease by a Mechanism Independent of Cross-Correction. Neuron 57 32375064
2015 Long-term Improvements in Lifespan and Pathology in CNS and PNS After BMT Plus One Intravenous Injection of AAVrh10-GALC in Twitcher Mice. Molecular therapy : the journal of the American Society of Gene Therapy 53 26329589
1996 Multiple mutations in the GALC gene in a patient with adult-onset Krabbe disease. Annals of neurology 52 8687180
2013 Missense mutation in mouse GALC mimics human gene defect and offers new insights into Krabbe disease. Human molecular genetics 49 23620143
2018 The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure. Nature communications 48 29323104
2016 Intrathecal administration of AAV/GALC vectors in 10-11-day-old twitcher mice improves survival and is enhanced by bone marrow transplant. Journal of neuroscience research 47 27638599
2014 Intravenous injection of AAVrh10-GALC after the neonatal period in twitcher mice results in significant expression in the central and peripheral nervous systems and improvement of clinical features. Molecular genetics and metabolism 43 25533112
1995 Elevated intracellular levels of cAMP induce olfactory ensheathing cells to express GAL-C and GFAP but not MBP. Glia 41 7544324
1993 Transient reversion of O4+ GalC- oligodendrocyte progenitor development in response to the phorbol ester TPA. Journal of neuroscience research 41 8423632
2016 Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 26865610
1996 Retroviral vector-mediated transfer of the galactocerebrosidase (GALC) cDNA leads to overexpression and transfer of GALC activity to neighboring cells. Biochemical and molecular medicine 38 8812733
2007 A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region. Human mutation 36 17579360
1994 Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization. Cytogenetics and cell genetics 36 8162701
2011 GALC deletions increase the risk of primary open-angle glaucoma: the role of Mendelian variants in complex disease. PloS one 34 22073273
2006 Design and optimization of lentiviral vectors for transfer of GALC expression in Twitcher brain. The journal of gene medicine 33 16732552
2002 Residual galactosylsphingosine (psychosine) beta-galactosidase activities and associated GALC mutations in late and very late onset Krabbe disease. Clinica chimica acta; international journal of clinical chemistry 31 11814461
2017 Heterozygote galactocerebrosidase (GALC) mutants have reduced remyelination and impaired myelin debris clearance following demyelinating injury. Human molecular genetics 29 28575206
1992 Stage specific, (O4+GalC-) isolated oligodendrocyte progenitors produce MBP+ myelin in vivo. Developmental neuroscience 29 1382941
2015 IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease. American journal of respiratory cell and molecular biology 28 25101718
2006 Suppression of galactosylceramidase (GALC) expression in the twitcher mouse model of globoid cell leukodystrophy (GLD) is caused by nonsense-mediated mRNA decay (NMD). Neurobiology of disease 28 16759875
2015 Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations. Journal of human genetics 27 26108143
1997 Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin. Journal of inherited metabolic disease 27 9266397
2023 GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease. Brain : a journal of neurology 26 36370000
1999 Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA. Neurochemical research 22 9972877
1993 Localization of the Krabbe disease gene (GALC) on chromosome 14 by multipoint linkage analysis. American journal of human genetics 22 8250040
2020 Pathogenic Variants in GALC Gene Correlate With Late Onset Krabbe Disease and Vision Loss: Case Series and Review of Literature. Frontiers in neurology 19 33178108
2013 Four novel GALC gene mutations in two Chinese patients with Krabbe disease. Gene 17 23462331
2021 Can early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT? BioImpacts : BI 15 33842284
2012 Isolated pyramidal tract impairment in the central nervous system of adult-onset Krabbe disease with novel mutations in the GALC gene. Brain & development 15 22959700
2005 GALC transduction leads to morphological improvement of the twitcher oligodendrocytes in vivo. Molecular genetics and metabolism 15 15781194
2020 GALC Triggers Tumorigenicity of Colorectal Cancer via Senescent Fibroblasts. Frontiers in oncology 14 32318333
2020 Adult-onset Krabbe disease due to a homozygous GALC mutation without abnormal signals on an MRI in a consanguineous family: A case report. Molecular genetics & genomic medicine 13 32677356
2017 Genomewide association study identifies GALC as susceptibility gene for mucous membrane pemphigoid. Experimental dermatology 11 29136295
2012 A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease. Gene 11 23276707
1997 Characterization of the GALC gene in three Japanese patients with adult-onset Krabbe disease. Genetic testing 10 10464649
2022 A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review. Neurogenetics 9 35013804
2020 Molecular dynamics simulations to decipher the structural and functional consequences of pathogenic missense mutations in the galactosylceramidase (GALC) protein causing Krabbe's disease. Journal of biomolecular structure & dynamics 9 32186243
1997 Analysis of the 5' flanking region of the human galactocerebrosidase (GALC) gene. Biochemical and molecular medicine 8 9441867
2024 Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years. Clinical genetics 7 38515343
2023 rAAV2-Mediated Restoration of GALC in Neural Stem Cells from Krabbe Patient-Derived iPSCs. Pharmaceuticals (Basel, Switzerland) 7 37111381
2023 Brain Targeted AAV1-GALC Gene Therapy Reduces Psychosine and Extends Lifespan in a Mouse Model of Krabbe Disease. Genes 7 37628569
2022 A novel GALC gene mutation associated with adult-onset Krabbe disease: a case report. Neurocase 7 35654103
2020 Novel GALC Mutations Cause Adult-Onset Krabbe Disease With Myelopathy in Two Chinese Families: Case Reports and Literature Review. Frontiers in neurology 7 32973651
2019 GALC mutations in Chinese patients with late-onset Krabbe disease: a case report. BMC neurology 7 31185936
2015 Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report. BMC pediatrics 7 26567009
2020 AAV-Mediated GALC Gene Therapy Rescues Alpha-Synucleinopathy in the Spinal Cord of a Leukodystrophic Lysosomal Storage Disease Mouse Model. Frontiers in cellular neuroscience 6 33424556
2017 Late onset Krabbe disease due to the new GALC p.Ala543Pro mutation, with intriguingly high residual GALC activity in vitro. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 6 28109651
2025 High Prevalence of GALC Gene Variants in Adults With Neurodegenerative Conditions. European journal of neurology 5 40391866
2015 GALC gene is downregulated by promoter hypermethylation in Epstein-Barr virus-associated nasopharyngeal carcinoma. Oncology reports 5 26178533
2024 Splicing mutations of GALC in adult patient with adult-onset Krabbe disease: case report and review of literature. Neurocase 4 38762762
2022 Production and characterization of human induced pluripotent stem cell line (PUMCi002-A) from a Krabbe patient related control to study disease mechanisms associated with GALC mutation. Stem cell research 4 36270068
2022 Reliable and Fast Genotyping Protocol for Galactosylceramidase (Galc) in the Twitcher (Twi) Mouse. Biomedicines 4 36551902
2020 Allele frequency analysis of GALC gene causing Krabbe disease in human and its codon usage. Gene 4 32304783
2018 Exonic deletions in GALC are frequent in Japanese globoid-cell leukodystrophy patients. Human genome variation 4 30323943
2015 Compound Galactosylceramidase Gene (GALC) Heterozygosity in a Boy with Infantile Krabbe Disease (KD). Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki) 4 27442402
2012 Array CGH improves detection of mutations in the GALC gene associated with Krabbe disease. Orphanet journal of rare diseases 4 22704718
2025 Brain accumulation of lactosylceramide characterizes GALC deficiency in a zebrafish model of Krabbe disease. Brain : a journal of neurology 3 40305757
2025 Investigating the Cellular Effects of GALC Dosing in Enzyme Replacement Therapy for Krabbe Disease Supports the Role of Nanomedicine. Advanced biology 3 40590240
2021 Compound heterozygous pathogenic variants in the GALC gene cause infant-onset Krabbe disease. Translational pediatrics 2 34765479
2025 Amelioration of Inflammation and Metabolic Blockage in GALC Deficient Mice After Enzyme Replacement Therapy via Extracellular Vesicles. International journal of nanomedicine 1 40692539
2025 Molecular Characterization of the GALC Mutation Thr112Ala Causing Krabbe Disease. International journal of molecular sciences 1 40943566
2025 Beyond Krabbe disease, the intriguing connection of galactocerebrosidase (GALC) with nervous system illness: A novel risk factor? Neuroscience 1 41086929
2024 Expression study of Krabbe Disease GALC missense variants - Insights from quantification profiles of residual enzyme activity, secretion and psychosine levels. bioRxiv : the preprint server for biology 1 39464077
2018 A novel homozygous GALC variant has been associated with Krabbe disease in a consanguineous family. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 30209698
2026 In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression. Genome medicine 0 42026681
2026 Molecular Dynamics Simulations of 4 GALC Variants Causing Krabbe Disease. Computational and structural biotechnology journal 0 42169729
2025 Abnormal Splicing of GALC Transcripts Underlies Unusual Cases of Krabbe Disease. Biomedicines 0 41463122
1999 [A case of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome with positive anti-galactocerebroside (Gal-C) IgM antibody]. Rinsho shinkeigaku = Clinical neurology 0 10424145

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