Affinage

CLN6

Ceroid-lipofuscinosis neuronal protein 6 · UniProt Q9NWW5

Length
311 aa
Mass
35.9 kDa
Annotated
2026-06-09
58 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLN6 is an endoplasmic reticulum-resident multi-pass membrane protein whose loss causes a variant of neuronal ceroid lipofuscinosis (vLINCL); it was identified as the causative gene through patient and nclf mouse mutations (PMID:11791207, PMID:11727201). The protein adopts a topology with an N-terminal cytoplasmic domain, seven transmembrane domains, and a luminal C-terminus, is not proteolytically processed, and forms homodimers; ER retention depends on its N-terminal cytosolic domain, transmembrane domains 6 and 7, and a dilysine motif (PMID:15010453, PMID:17453415). Although CLN6 resides in the ER, its function controls downstream lysosomal capacity: CLN6 forms an obligate complex with CLN8 (the EGRESS complex) that recruits soluble lysosomal enzymes at the ER to promote their transfer to the Golgi, with the second luminal loop of CLN6 mediating enzyme binding but being dispensable for CLN8 interaction (PMID:32597833). Consistent with this, CLN6 deficiency selectively reduces lysosomal levels of N-glycosylated soluble hydrolases and impairs their delivery without affecting cathepsin D synthesis or processing (PMID:15010453, PMID:34432360). CLN6 additionally exhibits an anti-aggregate activity in the ER, acting downstream of ER-anchored αB-crystallin and functionally coupling with pro-cathepsin D; this activity depends on the conformation of its luminal tail constrained by Pro297/299 (PMID:28476624, PMID:34380921, PMID:39032464). Disease-causing mutations act in a graded manner: some destabilize the protein and route it for proteasomal degradation through ERAD machinery (Derlin-1, p97, SEL1L) (PMID:18811591, PMID:20020536), while others reduce anti-aggregate activity to an extent that tracks with disease severity (PMID:32171521). CLN6 loss ultimately disrupts the autophagy-lysosome pathway, producing accumulation of LC3-II, ubiquitinated proteins, and p62-positive aggregates in neurons (PMID:22536393).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established the genetic basis of a neuronal ceroid lipofuscinosis subtype by identifying CLN6 as the disease gene and predicting it encodes a novel polytopic membrane protein of unknown function.

    Evidence Positional cloning and sequencing of patient and nclf mouse mutations; transmembrane topology prediction

    PMID:11727201 PMID:11791207

    Open questions at the time
    • No biochemical function assigned
    • Subcellular localization not determined
    • No homology to characterized proteins
  2. 2003 Medium

    Linked CLN6 disease to oxidative stress by detecting elevated MnSOD expression and activity in patient and sheep model tissues, an early correlative pathogenic feature.

    Evidence 2D electrophoresis, mass spectrometry, immunoblotting, and MnSOD enzyme activity assays in patient fibroblasts/brain and sheep OCL6 model

    PMID:12946273

    Open questions at the time
    • Correlative, not a direct CLN6-MnSOD mechanistic link
    • Cause vs consequence of disease unresolved
  3. 2004 High

    Resolved where CLN6 acts and how disease mutations behave by showing ER residence of wild-type CLN6, homodimer formation, lack of proteolytic processing, and ER retention of missense mutants.

    Evidence GFP-tagged and endogenous CLN6 immunofluorescence, cross-linking, glycosylation assay in HEK293/transfected cells

    PMID:15010453 PMID:15265688

    Open questions at the time
    • Molecular function of ER-resident CLN6 still unknown
    • No binding partners identified
  4. 2004 High

    Connected the ER-resident protein to lysosomal outcomes by showing CLN6 deficiency impairs lysosomal degradation of an endocytosed hydrolase without affecting cathepsin D biosynthesis.

    Evidence Pulse-chase, immunoprecipitation, and arylsulfatase A degradation assays in patient, sheep, and mouse cells

    PMID:15010453

    Open questions at the time
    • Mechanism linking ER protein to lysosomal function unexplained
    • Direct enzyme-trafficking role not yet demonstrated
  5. 2007 High

    Defined CLN6 membrane topology experimentally and identified the determinants of ER retention, grounding later structure-function dissection.

    Evidence Differential membrane permeabilization, mutagenesis, confocal imaging of fusion/deletion constructs in BHK and neuronal cells

    PMID:17453415

    Open questions at the time
    • Function of luminal C-terminus undefined
    • No interacting machinery identified
  6. 2009 Medium

    Provided the first protein partners and degradation logic: CLN6 mutants are turned over by ERAD machinery, and CLN6 interacts with CRMP-2 with consequences for neuronal maturation.

    Evidence Co-IP with Derlin-1/p97 and CRMP-2, SEL1L knockdown rescue, proteasome inhibition, hippocampal neuron and DRG assays

    PMID:18811591 PMID:19235893

    Open questions at the time
    • CRMP-2 interaction from single lab without reciprocal validation
    • Functional significance of CRMP-2 binding for lysosomal role unclear
  7. 2010 Medium

    Showed that disease mutations destabilize CLN6 to differing degrees, establishing graded protein turnover as a determinant of mutant behavior.

    Evidence Pulse-chase with proteasomal/lysosomal inhibitors across multiple mutations in patient and transfected cells

    PMID:20020536

    Open questions at the time
    • Quantitative link to disease severity not established here
    • Single lab
  8. 2012 Medium

    Demonstrated that CLN6 loss disrupts the autophagy-lysosome pathway in vivo, attributing pathology to defective autophagosome-lysosome clearance rather than ER stress.

    Evidence Western blot for LC3-II/ubiquitin/p62, immunofluorescence, ER stress marker analysis across nclf mouse brain regions and ages

    PMID:22536393

    Open questions at the time
    • Direct evidence for fusion defect indirect
    • Single model/lab
  9. 2017 Medium

    Revealed an ER anti-aggregate function for CLN6 as a downstream effector of ER-anchored αB-crystallin, broadening its role beyond enzyme trafficking.

    Evidence Pulldown, siRNA knockdown, overexpression, and αBC R120G aggregation assays with lysosomal inhibition in HeLa cells

    PMID:28476624

    Open questions at the time
    • Mechanism of aggregate suppression unresolved
    • Relationship to trafficking function unclear
    • Single lab
  10. 2020 High

    Defined the central trafficking mechanism: CLN6 and CLN8 form the obligate EGRESS complex that recruits lysosomal enzymes at the ER for Golgi transfer, with CLN6's second luminal loop binding enzymes.

    Evidence Co-IP, luminal loop mutagenesis, in vitro/in vivo trafficking assays, double-knockout epistasis in mice

    PMID:32597833

    Open questions at the time
    • Structural basis of enzyme recognition unknown
    • How EGRESS releases cargo at the Golgi undefined
  11. 2020 Medium

    Connected mutant anti-aggregate activity to clinical severity, showing graded loss of function across mutations from late-infantile to adult onset.

    Evidence Cell-based αBC aggregation assays with multiple CLN6 mutants in HeLa cells

    PMID:32171521

    Open questions at the time
    • Based on overexpression
    • Severity correlation inferred, not tested in patients
  12. 2021 Medium

    Mapped the conformational requirement of CLN6's luminal tail, implicating Pro297/299 in maintaining the anti-aggregate-competent conformation.

    Evidence Alanine substitution and truncation mutagenesis in cell-based aggregation assays in HeLa cells

    PMID:34380921

    Open questions at the time
    • No direct structural data on luminal tail conformation
    • Single lab cell-based assay
  13. 2021 Medium

    Specified the affected cargo class by showing CLN6 loss selectively reduces N-glycosylated soluble lysosomal hydrolases, including other NCL proteins.

    Evidence Comparative lysosomal proteomics with Western blot and enzyme assay validation in nclf mouse liver

    PMID:34432360

    Open questions at the time
    • Tissue-specific generality untested
    • Single lab
  14. 2024 Medium

    Identified pro-cathepsin D as a functional partner in CLN6-dependent ER anti-aggregation, requiring pro-peptide integrity and acting before lysosomal processing.

    Evidence Co-IP of ER-anchored αBC partners, CTSD variant overexpression, CLN6 knockdown, aggregation assay in HeLa cells

    PMID:39032464

    Open questions at the time
    • Direct CLN6-proCTSD binding interface not defined
    • Single lab
  15. 2024 Low

    Confirmed lysosomal trafficking deficits in a human patient-derived neuron model, showing reduced TPP1 activity, LAMP1 accumulation, and enlarged Golgi.

    Evidence CLN6-iPSC-derived neurons with TPP1 activity assay, LAMP1 immunofluorescence, Golgi morphology (preprint)

    PMID:38352418

    Open questions at the time
    • Preprint, not peer-reviewed
    • Phenotypic characterization without mechanistic dissection
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CLN6's enzyme-trafficking (EGRESS) function and its ER anti-aggregate activity are mechanistically integrated, and the structural basis for cargo recognition and luminal-tail conformation, remain unresolved.
  • No high-resolution structure of CLN6 or the EGRESS complex
  • Unclear whether anti-aggregate and trafficking roles are separable
  • Mechanism of cargo release at the Golgi undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-9609507 Protein localization 3 R-HSA-5653656 Vesicle-mediated transport 1 R-HSA-9612973 Autophagy 1
Partners
CLN8CRMP-2CRYABCTSDDERLIN-1P97SEL1L
Complex memberships
EGRESS (CLN6-CLN8) complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CLN6 encodes a novel ~36 kDa transmembrane protein with predicted membrane-spanning domains; mutations in human patients (stop codon, codon deletion) and a frameshift in the nclf mouse cause neuronal ceroid lipofuscinosis, establishing CLN6 as the causative gene for vLINCL. Positional cloning, haplotype analysis, DNA sequencing of patients and nclf mouse American journal of human genetics High 11727201 11791207
2001 CLN6 encodes a 311-amino acid protein with seven predicted transmembrane domains, conserved across vertebrates, with no homology to proteins of known function; a disease mutation affecting a conserved residue in the predicted third hydrophilic loop suggests functional importance of that domain. Sequence analysis, transmembrane topology prediction, mutation mapping American journal of human genetics Medium 11727201 11791207
2004 CLN6 protein resides in the endoplasmic reticulum (ER); CLN6-GFP fusion expressed in HEK293 cells co-localizes with ER markers, and five disease-causing CLN6 missense mutations are retained in the ER without trafficking to Golgi or lysosomes. Immunofluorescence microscopy, GFP-tagged CLN6 expression, Western blotting with CLN6-specific antisera Experimental cell research High 15010453 15265688
2004 CLN6 does not undergo proteolytic processing and forms homodimers (detected by cross-linking); it is retained in the ER with no co-localization with cis-Golgi or lysosomal markers. The ER translocation and proper folding of a mutant CLN6 polypeptide was confirmed by N-linked glycosylation of an engineered mutant. Transient transfection, immunoblot, cross-linking experiments, double immunofluorescence microscopy, N-linked glycosylation assay The Journal of biological chemistry High 15010453
2004 CLN6 deficiency (in patient fibroblasts and sheep/mouse models) does not affect synthesis, sorting, or proteolytic processing of cathepsin D, but strongly reduces lysosomal degradation of endocytosed arylsulfatase A, linking the ER-resident CLN6 protein to downstream lysosomal function. Pulse-chase labeling, immunoprecipitation of cathepsin D, degradation assay of endocytosed arylsulfatase A in patient and animal-model cell lines The Journal of biological chemistry High 15010453
2007 CLN6 topology was established experimentally: N-terminal cytoplasmic domain, seven transmembrane domains, and a luminal C-terminus. ER retention depends on both the N-terminal cytosolic domain and transmembrane domains 6 and 7; deletion of a dilysine motif partially impairs ER localization; CLN6 homodimerization may also contribute to ER retention. Differential membrane permeabilization with specific detergents and antibodies, mutational analysis, confocal immunofluorescence microscopy of fusion/deletion constructs in BHK and neuronal cells Molecular membrane biology High 17453415
2009 CLN6 physically interacts with CRMP-2 (collapsin response mediator protein-2); in nclf mice lacking functional CLN6, CRMP-2 protein levels are reduced in the brain (particularly thalamus), and hippocampal neurons from nclf mice show impaired maturation and increased cell death in culture. Co-immunoprecipitation (pulldown), Western blotting, hippocampal neuron culture, dorsal root ganglion repulsion assay Journal of neuroscience research Medium 19235893
2009 CLN6 disease-associated mutants (G123D and M241T) undergo rapid proteasome-mediated degradation and associate with ER extraction machinery components Derlin-1 and p97; knockdown of SEL1L (an E3 ubiquitin ligase complex member) rescues significant amounts of mutant Cln6 polypeptides, implicating ER quality control/ERAD in CLN6 mutant turnover. Co-immunoprecipitation, siRNA knockdown of SEL1L, proteasome inhibitor experiments in neuronal-derived human cells Bioscience reports Medium 18811591
2010 Three CLN6 patient mutations (p.Gly123Asp, p.Ile154del, p.Arg106ProfsX26) reduce the rate of synthesis and stability of CLN6 protein in a mutation-dependent manner; the truncated p.Arg106ProfsX26 mutant (equivalent to nclf mouse mutation) is rapidly degraded primarily by the proteasome and partially by lysosomal proteases; none of the mutations prevented CLN6 dimerization. Pulse-chase labeling, proteasomal and lysosomal inhibitor treatment, expression studies in patient and transfected cells Human mutation Medium 20020536
2012 In nclf mouse brains, CLN6 deficiency leads to age-dependent increases in LC3-II, ubiquitinated proteins, and neuronal p62-positive aggregates, indicating disruption of the autophagy-lysosome pathway; this is most likely due to defective autophagosome-lysosome fusion rather than ER stress or unfolded protein response activation. The mutant Cln6 protein with reduced half-life is degraded by the proteasome. Western blotting for LC3-II, ubiquitin, p62; immunofluorescence; proteasomal inhibitor assays; analysis of ER stress markers across brain regions and developmental time points in nclf mice PloS one Medium 22536393
2017 CLN6, an ER transmembrane protein, physically interacts with ER-anchored αB-crystallin (TMαBC) and operates as a downstream effector of TMαBC's anti-aggregate activity; CLN6 knockdown attenuates TMαBC's ability to prevent R120G αBC aggregation, while CLN6 overexpression enhances it; CLN6 directly interacts with the aggregation-prone R120G αBC mutant and suppresses its aggregation, dependent on an intact autophagy-lysosome system. Co-immunoprecipitation/pulldown (isolation of TMαBC-binding proteins), siRNA knockdown, overexpression in HeLa cells, aggregate formation assay, lysosomal inhibitor treatment Biochemical and biophysical research communications Medium 28476624
2020 CLN6 forms an obligate complex with CLN8 at the ER (termed EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system) that recruits lysosomal enzymes at the ER to promote their Golgi transfer; the second luminal loop of CLN6 is required for interaction with lysosomal enzymes but not for interaction with CLN8; CLN6 deficiency results in inefficient ER export of lysosomal enzymes and reduced lysosomal enzyme levels; mice lacking both CLN6 and CLN8 show no aggravated pathology compared to single knockouts, indicating EGRESS functions as a single unit. Co-immunoprecipitation, protein interaction assays, CLN6 mutagenesis (luminal loop deletions), trafficking assays in vitro and in vivo, double-knockout mouse analysis The Journal of clinical investigation High 32597833
2020 CLN6 disease-causing mutations reduce CLN6's anti-aggregate activity in a graded, mutation-dependent manner; the truncating Arg106ProfsX mutant (late infantile onset) abolishes anti-aggregate activity against all αBC mutants tested, while Arg149Cys and Arg149His adult-onset mutants retain partial activity; this graded reduction is proposed to govern disease severity. Overexpression of CLN6 mutants in cell-based aggregation assay using αB-crystallin mutants as substrates Biochemical and biophysical research communications Medium 32171521
2021 CLN6's luminal tail (C-terminal region) participates in a conformational mechanism: the S132CfsX18 truncated mutant nullifies the anti-aggregate activity of the P299L missense CLN6 mutant (but not wild-type CLN6); resistance of wild-type CLN6 to the truncated mutant is lost when amino acids 297-301 (including Pro297/299) are mutated to alanine, suggesting Pro297/299 maintain a conformational constraint on the luminal tail needed for anti-aggregate activity. Cell-based aggregation assay, alanine substitution mutagenesis, deletion constructs expressed in HeLa cells Biomedical research (Tokyo, Japan) Medium 34380921
2021 CLN6 deficiency causes selective reduction in specific lysosomal protein amounts, particularly N-glycosylated soluble hydrolases including several other NCL family proteins, as shown by comparative proteomics of isolated lysosomal fractions from nclf mouse liver, verified by Western blotting and enzymatic assays. Lysosomal fraction isolation, comparative proteomics (mass spectrometry), Western blotting, enzymatic activity assays in nclf mouse liver Proteomics Medium 34432360
2024 Pro-cathepsin D (proCTSD) prevents protein aggregation through functional association with CLN6 in the ER microenvironment: proCTSD was identified as a binding partner of ER-anchored αBC; CLN6 depletion abolishes proCTSD's anti-aggregate activity; the pro-peptide integrity of CTSD is required for this activity, and the activity occurs before lysosomal processing of CTSD. Co-immunoprecipitation (isolation of ER-anchored αBC binding proteins), overexpression of CTSD variants including an ER-retained mutant, CLN6 knockdown, aggregate formation assay in HeLa cells Molecular genetics and metabolism Medium 39032464
2003 Enhanced expression and activity of manganese-dependent superoxide dismutase (MnSOD) was found in fibroblasts and brain of human CLN6 patients and sheep OCL6 model by 2D electrophoresis, MS, immunoblotting, and enzyme activity assays, suggesting oxidative stress as a feature of CLN6 disease pathogenesis. 2D electrophoresis, mass spectrometry, immunoblotting, MnSOD enzyme activity assay, confocal fluorescence microscopy, immunohistochemistry The Biochemical journal Medium 12946273
2024 CLN6-IPSC-derived neurons show decreased tripeptidyl peptidase-1 (TPP1) activity and increased LAMP1+ signal in cell bodies and neurites, confirming CLN6's role in lysosomal enzyme trafficking; CLN6-deficient neurons also show increased Golgi area, consistent with impaired ER-to-Golgi transfer of lysosomal enzymes. IPSC differentiation into neurons, enzyme activity assay (TPP1), immunofluorescence (LAMP1), Golgi morphology analysis bioRxivpreprint Low 38352418

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. American journal of human genetics 165 11791207
2001 The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein. American journal of human genetics 147 11727201
2011 Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. American journal of human genetics 108 21549341
1998 Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9. American journal of medical genetics 104 9600738
2004 CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. Experimental cell research 89 15265688
2004 Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A. The Journal of biological chemistry 78 15010453
2020 A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer. The Journal of clinical investigation 70 32597833
2003 Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis. Human mutation 65 12815591
2006 A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA. Biochimica et biophysica acta 61 17046213
2012 Disruption of the autophagy-lysosome pathway is involved in neuropathology of the nclf mouse model of neuronal ceroid lipofuscinosis. PloS one 59 22536393
2013 Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation. PloS one 53 24124525
2007 Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6. Molecular membrane biology 41 17453415
2019 Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease. Molecular therapy : the journal of the American Society of Gene Therapy 40 31331814
2003 Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis. Human mutation 37 12673792
2018 Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells. Molecular therapy : the journal of the American Society of Gene Therapy 34 29606505
2009 Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2. Journal of neuroscience research 33 19235893
2019 Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features. Brain : a journal of neurology 30 30561534
2003 Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues. The Biochemical journal 30 12946273
2013 Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis. Biology open 25 23789114
2013 Apoptotic photoreceptor loss and altered expression of lysosomal proteins in the nclf mouse model of neuronal ceroid lipofuscinosis. Investigative ophthalmology & visual science 25 24084090
2013 Increased zinc and manganese in parallel with neurodegeneration, synaptic protein changes and activation of Akt/GSK3 signaling in ovine CLN6 neuronal ceroid lipofuscinosis. PloS one 24 23516525
2010 Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. Human mutation 23 20020536
2019 Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease. Human molecular genetics 20 31807779
2009 Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner. Bioscience reports 19 18811591
2015 Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PloS one 18 25992714
2012 Mutation of the CLN6 gene in teenage-onset progressive myoclonus epilepsy. Pediatric neurology 17 22883287
2021 Intracranial delivery of AAV9 gene therapy partially prevents retinal degeneration and visual deficits in CLN6-Batten disease mice. Molecular therapy. Methods & clinical development 15 33665223
2018 Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients. Molecular genetics and metabolism 11 30528883
2011 High expression of disease-related Cln6 in the cerebral cortex, purkinje cells, dentate gyrus, and hippocampal ca1 neurons. Journal of neuroscience research 11 22012656
2022 Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience. Orphanet journal of rare diseases 10 35012600
2021 A Novel CLN6 Variant Associated With Juvenile Neuronal Ceroid Lipofuscinosis in Patients With Absence of Visual Loss as a Presenting Feature. Frontiers in genetics 10 34868216
2023 Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease). Developmental neurobiology 9 37246363
2021 CLN6 deficiency causes selective changes in the lysosomal protein composition. Proteomics 9 34432360
2023 Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis. Brain communications 8 36632184
2021 An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease. Journal of neurochemistry 8 33368303
2017 Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity. Biochemical and biophysical research communications 8 28476624
1999 Progress toward the cloning of CLN6, the gene underlying a variant LINCL. Molecular genetics and metabolism 8 10191124
2021 Electroretinography data from ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses. Data in brief 7 34141843
2019 Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation. Brain & development 7 31029456
2020 Implications of graded reductions in CLN6's anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses. Biochemical and biophysical research communications 6 32171521
2023 Neuronal progenitor cells-based metabolomics study reveals dysregulated lipid metabolism and identifies putative biomarkers for CLN6 disease. Scientific reports 5 37899458
2021 CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses. Biomedical research (Tokyo, Japan) 4 34380921
2020 Moyamoya and progressive myoclonic epilepsy secondary to CLN6 bi-allelic mutations - A previously unreported association. Epilepsy & behavior reports 4 33024953
2012 CLN6 p.I154del mutation causing late infantile neuronal ceroid lipofuscinosis in a large consanguineous Moroccan family. Indian journal of pediatrics 4 23180398
2024 Cellular Modeling of CLN6 with IPSC-derived Neurons and Glia. bioRxiv : the preprint server for biology 2 38352418
2024 Neuronal ceroid lipofuscinosis in a Schapendoes dog is caused by a missense variant in CLN6. Animal genetics 2 38866396
2024 Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6. Genes 2 38927597
2021 p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis. Clinica chimica acta; international journal of clinical chemistry 2 34597687
2025 Expanded Phenotype of the Cln6 Mouse Model. Cells 1 40358187
2024 A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 38771523
2024 CLN6-related continuum phenotype caused by aberrant splicing. Epilepsia open 1 39718800
2023 Rare adult neuronal ceroid lipofuscinosis associated with CLN6 gene mutations: A case report. World journal of clinical cases 1 37383919
2023 Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families. Epilepsy research 1 38382230
2022 Aggregation chimeras provide evidence of in vivo intercellular correction in ovine CLN6 neuronal ceroid lipofuscinosis (Batten disease). PloS one 1 35404973
2026 A Flupirtine Benzyl Carbamate Improves Neurocognitive Deficits and Molecular Pathology in the Cln6 Mouse. Cells 0 41827875
2025 Diagnostic analysis of adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation: a case report. Clinical parkinsonism & related disorders 0 40823674
2024 Pro-cathepsin D prevents aberrant protein aggregation dependent on endoplasmic reticulum protein CLN6. Molecular genetics and metabolism 0 39032464
2022 Juvenile-Onset Kufs Disease in a Chinese Consanguineous Family due to CLN6 Mutation. Neuro-degenerative diseases 0 35609511

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