Affinage

CLN5

Bis(monoacylglycero)phosphate synthase CLN5 · UniProt O75503

Length
358 aa
Mass
41.5 kDa
Annotated
2026-06-09
89 papers in source corpus 24 papers cited in narrative 24 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

CLN5 encodes a soluble lysosomal glycoprotein whose loss causes Finnish variant late infantile neuronal ceroid lipofuscinosis, a phenotype traced to multiple disease-causing mutations identified at its original positional cloning (PMID:9662406). Although originally predicted to be a transmembrane protein, CLN5 is synthesized as a type II transmembrane precursor that is converted to a mature soluble lysosomal glycoprotein anchored to the luminal membrane leaflet by an amphipathic helix, with the cytoplasmic and transmembrane segments removed by SPPL3-mediated intramembrane proteolysis to yield mature residues 93–407 (PMID:11971870, PMID:24038957, PMID:28442266). N-glycosylation governs both folding and trafficking, with distinct glycosylation sites required for ER exit versus lysosomal delivery, and CLN5 can reach lysosomes by a mannose-6-phosphate-receptor-independent route (PMID:24058541, PMID:20052765); pathogenic mutants are mistargeted and retained in the ER for proteasomal degradation (PMID:24038957, PMID:19309691). CLN5 carries two enzymatic activities: it is the lysosomal BMP synthase that builds bis(monoacylglycero)phosphate by an energy-independent base-exchange reaction between two lysophosphatidylglycerol molecules (PMID:37708259), and it is a cysteine palmitoyl thioesterase whose papain-like N1pC/P60 fold uses a Cys280–His166–Glu183 catalytic triad to mediate S-depalmitoylation (PMID:35427157, PMID:38055807). Functionally, CLN5 controls endolysosomal sorting and fusion: it binds the sorting receptors sortilin and CI-MPR and sustains active Rab7 to support retromer recruitment at endosomes (PMID:22431521), and it acts with CLN3 to regulate RAB7A-effector interactions and endolysosome fusion, autophagy, and degradative flux (PMID:34060589). CLN5 physically interacts with the broader NCL protein network (CLN1/PPT1, CLN2/TPP1, CLN3, CLN6, CLN8) (PMID:12134079, PMID:19941651), and its abundance is set by CRL3-KCTD7-mediated ubiquitination and proteasomal degradation, with KCTD7 disease mutations causing pathological CLN5 accumulation that disrupts CLN6/CLN8-dependent lysosomal enzyme trafficking (PMID:35921411). Consistent with these roles, CLN5 deficiency produces lipid imbalance, impaired lysosomal motility and acidification in neurons, mitochondrial dysfunction, and dysregulated autophagy (PMID:37708259, PMID:34680045, PMID:32257390, PMID:30655561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Established CLN5 as a disease gene by linking its mutation to a defined neurodegenerative lysosomal storage disorder, providing the entry point for all mechanistic work.

    Evidence Positional cloning and patient DNA sequencing in Finnish variant late infantile neuronal ceroid lipofuscinosis

    PMID:9662406

    Open questions at the time
    • The original cloning predicted a transmembrane topology that was later overturned
    • No molecular function assigned at identification
  2. 2002 High

    Resolved the basic nature and protein interactions of CLN5, showing it is a soluble lysosomal glycoprotein rather than an integral membrane protein and that it engages other NCL proteins.

    Evidence Confocal microscopy, deglycosylation, immunoprecipitation in BHK-21 cells, and reciprocal Co-IP/in vitro binding with disease-mutation validation

    PMID:11971870 PMID:12134079

    Open questions at the time
    • Did not define the protease producing the soluble form
    • Functional consequence of CLN2/CLN3 binding unresolved
  3. 2009 Medium

    Expanded the NCL interaction network and showed cross-rescue of trafficking, establishing CLN5 as a hub among ceroid lipofuscinosis proteins.

    Evidence Co-IP, localization, and co-expression rescue assays plus patient-mutant ER retention in patient-derived cells

    PMID:19309691 PMID:19941651

    Open questions at the time
    • Interactions largely single-lab Co-IP without reconstitution
    • Stoichiometry and directness of multi-NCL binding unclear
  4. 2012 High

    Defined a trafficking-regulatory function: CLN5 supports retromer-dependent recycling of lysosomal sorting receptors by maintaining active Rab7.

    Evidence Co-IP with sortilin, siRNA depletion in HeLa cells with receptor degradation and Rab7-GTP readouts

    PMID:22431521

    Open questions at the time
    • Mechanism by which CLN5 sustains Rab7-GTP not defined
    • Whether enzymatic activity underlies the trafficking effect not addressed
  5. 2013 High

    Reconciled topology with maturation by showing CLN5 is a type II transmembrane precursor anchored after cleavage by an amphipathic helix, with N-glycosylation partitioned between folding and trafficking roles.

    Evidence Topology mapping with epitope tags, membrane solubility assays, systematic N-glycosylation site mutagenesis, proteasome inhibition

    PMID:24038957 PMID:24058541

    Open questions at the time
    • Identity of the cleaving protease still unknown at this stage
    • Functional output of mature CLN5 not yet defined
  6. 2017 High

    Identified SPPL3 as the intramembrane protease generating mature soluble CLN5, closing the maturation pathway.

    Evidence Tagged CLN5 constructs with SPPL family overexpression/knockdown and fragment characterization by Western blot

    PMID:28442266 PMID:29128403

    Open questions at the time
    • Glycoside hydrolase activity reported but substrate identity unresolved
    • Relationship between SPPL3 processing and downstream function unaddressed
  7. 2021 Medium

    Placed CLN5 in an endolysosomal complex with CLN3 that regulates RAB7A-effector interactions, linking it directly to endolysosome fusion and autophagy.

    Evidence CLN5 knockout/knockdown in HeLa cells, Co-IP of CLN3-RAB7A-effector axis, fusion and autophagy flux assays

    PMID:34060589

    Open questions at the time
    • Direct biochemical architecture of the CLN5-CLN3 complex not solved
    • Single-lab functional dataset
  8. 2022 High

    Assigned a defined catalytic activity—cysteine palmitoyl thioesterase—via crystal structure and catalytic-residue mutagenesis, and showed CLN5 abundance is controlled by CRL3-KCTD7 ubiquitination.

    Evidence Crystal structure, H166A/C280A mutagenesis, fluorescent thioesterase assay, and ubiquitination assays with KCTD7 patient-mutation cell lines

    PMID:35427157 PMID:35921411

    Open questions at the time
    • Physiological palmitoylated substrates of CLN5 thioesterase activity not identified
    • How thioesterase activity relates to trafficking phenotypes unresolved
  9. 2023 High

    Established CLN5 as the lysosomal BMP synthase and detailed the chemical mechanism of its second activity, giving the protein two distinct enzymatic functions.

    Evidence BMPS-deficient cells with lipidomics, in vitro reconstitution of LPG base-exchange, and QM/MM mechanistic analysis of S-depalmitoylation

    PMID:37708259 PMID:38055807

    Open questions at the time
    • Whether BMP synthase and thioesterase activities use the same active site is not established
    • Which activity drives the disease phenotype unresolved
  10. 2023 Medium

    Characterized the cellular consequences of CLN5 loss across organelles, connecting the gene to lipid imbalance, neuronal lysosomal dysfunction, mitochondrial defects, and altered autophagy.

    Evidence iPSC-neuron CRISPRi imaging, mitochondrial proteomics in KO cells and Cln5-/- mouse cortex, autophagy flux and SNCA rescue, and Dictyostelium secretion genetics

    PMID:23160995 PMID:30655561 PMID:32257390 PMID:34680045 PMID:38272448

    Open questions at the time
    • Causal ordering between primary enzymatic loss and downstream organelle phenotypes unclear
    • Many phenotypes are single-lab or model-organism observations

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CLN5's two enzymatic activities (BMP synthase and depalmitoylase) and its trafficking-regulatory role are mechanistically integrated, and which is the primary driver of neurodegeneration.
  • No defined physiological thioesterase substrate
  • No structural model linking active site to BMP synthesis
  • Disease-relevant primary defect unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0016740 transferase activity 1
Localization
GO:0005764 lysosome 3 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 2
Partners
CLN3CLN6CLN8KCTD7PPT1RAB7ASORT1TPP1
Complex memberships
CLN5–CLN3 endolysosomal complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CLN5 was identified by positional cloning as a novel gene encoding a putative transmembrane protein; three disease-causing mutations (one deletion, one nonsense, one missense) were identified in patients with Finnish variant late infantile neuronal ceroid lipofuscinosis. Positional cloning, sequence analysis of patient DNA samples Nature genetics High 9662406
2002 CLN5 protein is predominantly targeted to lysosomes and is a soluble lysosomal glycoprotein (~60 kDa glycosylated, ~38-40 kDa after deglycosylation), not an integral transmembrane protein as previously predicted. The most common Finnish vLINCL mutation blocked lysosomal targeting. Confocal immunofluorescence microscopy, immunoprecipitation, deglycosylation assays (Endo H, PNGase F) in transiently transfected BHK-21 cells Human molecular genetics High 11971870
2002 CLN5 directly interacts with CLN2 and CLN3 proteins based on co-immunoprecipitation and in vitro binding assays. Disease mutations in CLN5 abolished interaction with CLN2 but not CLN3. CLN5 is synthesized as four precursor forms from alternative initiator methionines; the longest membrane-associated form mediates interactions with CLN proteins. Co-immunoprecipitation, in vitro binding assays, Western blotting, mutagenesis Molecular biology of the cell High 12134079
2009 CLN5 interacts with multiple NCL proteins: CLN1/PPT1, CLN2/TPP1, CLN3, CLN6, and CLN8. Over-expression of PPT1 can facilitate lysosomal transport of the mutated CLN5(FinMajor) protein normally retained in ER/Golgi. CLN5 also binds the F1-ATPase, a known PPT1-interacting partner. Co-immunoprecipitation, intracellular localization studies, co-expression assays BMC cell biology Medium 19941651
2012 CLN5 interacts with the lysosomal sorting receptor sortilin. CLN5 depletion causes degradation of sortilin and the cation-independent mannose 6-phosphate receptor (CI-MPR) in lysosomes due to defective retromer recruitment at endosomes. CLN5 depletion also reduces active (GTP-loaded) Rab7, which is required for retromer recruitment. Co-immunoprecipitation, siRNA-mediated depletion in HeLa cells, Western blotting, fluorescence microscopy Molecular and cellular biology High 22431521
2013 CLN5 has eight functional N-glycosylation sites; glycosylation at specific asparagines (N179, N252, N304, N320) is required for proper protein folding (mutants retained in ER), while glycosylation at N401 is required for lysosomal trafficking (mutant mislocalizes to Golgi). Patient mutant N192S reaches the lysosome, suggesting a functional defect at that location. Site-directed mutagenesis of N-glycosylation sites, localization studies by fluorescence microscopy in transfected cells PloS one High 24058541
2013 CLN5 is synthesized as a type II transmembrane glycoprotein with a cytoplasmic N-terminus, one transmembrane segment, and a large luminal C-terminal domain containing an amphipathic helix (AH). The cytoplasmic and TM domains are removed by signal-peptide cleavage, and the mature CLN5 is anchored to the membrane lumen via the AH. CLN5 pathological mutants lacking the AH are retained in the ER and degraded by the proteasome. Epitope-tagged CLN5 topology mapping, membrane solubility assays, localization by fluorescence microscopy, proteasome inhibitor experiments Human mutation High 24038957
2015 CLN5 undergoes proteolytic cleavage at its C-terminus in an acidic compartment, requiring a cysteine protease. A ~60 kDa proprotein form is processed to a ~56 kDa mature form post-translationally. Processing can occur as early as the trans-Golgi network. Cycloheximide chase analysis, pharmacological protease inhibitors, transient transfection of patient and glycosylation mutants, Western blotting Experimental cell research Medium 26342652
2017 CLN5 is cleaved by SPPL3 (a member of the SPP/SPPL intramembrane protease family) from a type II transmembrane precursor into a mature soluble protein consisting of residues 93–407. The remaining N-terminal fragment is subsequently cleaved by SPPL3 and SPPL2b and degraded by the proteasome. Expression of tagged CLN5 constructs, overexpression/knockdown of SPPL family members, Western blotting, co-expression assays Experimental cell research High 28442266
2017 Both Dictyostelium Cln5 and human CLN5 function as glycoside hydrolases, as shown using fluorescent enzyme substrates. Dictyostelium Cln5 is secreted during growth and starvation and interacts with proteins involved in metabolism, catabolism, proteolysis, and hydrolysis including other NCL-like proteins (Tpp1/Cln2, cathepsin D/Cln10). Glycoside hydrolase fluorescent substrate assays, immunoprecipitation coupled with mass spectrometry, secretion assays, GFP fusion localization Cellular signalling Medium 29128403
2018 An AD-associated CLN5 variant (p.Asn320Ser) causes glycosylation defects, ER retention, and reduced delivery to the endolysosomal compartment. This variant reduces normal processing of cathepsin D and decreases levels of full-length amyloid precursor protein (APP), consistent with a defect in retromer-dependent trafficking. Expression of variant CLN5 in cells, Western blotting for glycosylation, immunofluorescence for localization, cathepsin D maturation assay, APP level measurement Molecular and cellular biology Medium 30037983
2021 CLN5 and CLN3 function as an endolysosomal complex. CLN5 deletion results in impaired endolysosome fusion events, delayed degradation of endocytic proteins, and defective autophagy. CLN5 modulates these pathways by regulating downstream interactions between CLN3, RAB7A, and a subset of RAB7A effectors. CLN5 knockout/knockdown in HeLa cells, Co-immunoprecipitation for CLN3-RAB7A-effector interactions, endolysosome fusion assays, autophagy flux assays The Biochemical journal Medium 34060589
2022 CLN5 (Cln5) has cysteine palmitoyl thioesterase (S-depalmitoylation) activity. The crystal structure revealed homology to the catalytic domain of the N1pC/P60 superfamily of papain-like enzymes, and mutational analysis showed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for thioesterase activity. CLN5-deficient neuronal progenitor cells show reduced thioesterase activity. Crystal structure determination, site-directed mutagenesis (H166A, C280A), fluorescent substrate (DDP-5) thioesterase assay, CLN5-deficient cell line thioesterase activity measurement Science advances High 35427157
2022 The CRL3-KCTD7 ubiquitin ligase complex targets CLN5 for ubiquitination and proteasomal degradation. NCL patient-derived KCTD7 mutations disrupt KCTD7–CUL3 or KCTD7–CLN5 interactions, causing excessive CLN5 accumulation. Accumulated CLN5 disrupts the interaction between CLN6/CLN8 and lysosomal enzymes at the ER, impairing ER-to-Golgi trafficking of lysosomal enzymes. Co-immunoprecipitation, ubiquitination assays, KCTD7 knockout/patient-mutation cell lines, Western blotting for lysosomal enzyme trafficking Science advances High 35921411
2023 CLN5 is the lysosomal BMP synthase (BMPS). CLN5-deficient cells exhibit massive accumulation of the BMP precursor lysophosphatidylglycerol (LPG), depletion of BMP species, and dysfunctional lipid metabolism. Mechanistically, CLN5 mediates BMP synthesis through an energy-independent base exchange reaction between two LPG molecules, with increased activity on BMP-laden vesicles. BMPS-deficient cell generation, lipidomic profiling (LPG and BMP quantitation), in vitro enzymatic assay reconstitution with LPG substrates, BMP-laden vesicle activity assay Science (New York, N.Y.) High 37708259
2023 QM/MM computational analysis of the CLN5 crystal structure confirmed that S-depalmitoylation proceeds via a catalytic triad Cys280–His166–Glu183, and that S-depalmitoylation (barrier ~26.1 kcal/mol) is the rate-limiting step compared to the preceding S-palmitoylation step (~25.3 kcal/mol). QM/MM calculations at ωB97X-D/6-31G(d,p):AMBER level, NBO charge analysis, local mode stretching force constants Journal of the American Chemical Society Medium 38055807
2010 CLN5 undergoes proteolytic cleavage to generate a mature polypeptide transported to lysosomes. CLN5 can also traffic to lysosomes via a mannose-6-phosphate receptor-independent pathway. All analyzed disease-causing mutations disrupt lysosomal trafficking of CLN5 proteins, but the degree of lysosomal mistargeting does not correlate with disease onset. Transient and stable expression in HeLa cells, pulse-chase metabolic labeling, immunofluorescence localization, M6P receptor blocking experiments Human mutation Medium 20052765
2009 In cells lacking CLN5, lysosomal movement/trafficking is impaired in human cortical-like glutamatergic neurons, and lysosomal enzyme activity and acidic organelle content are reduced. CRISPRi knockdown of CLN5 in iPSC-derived human neurons, live-cell imaging of lysosomal movement, microscopy and flow cytometry for acidic organelles, lysosomal enzyme activity assay Biomolecules Medium 34680045
2020 CLN5 loss leads to mitochondrial dysfunction and impaired mitophagy. A mitochondria-focused proteomics approach in CLN5 KO cells and Cln5-/- mouse cerebral cortex revealed impairment of mitochondrial respiratory function and activation of mitophagy pathways, correlated with disease progression. Quantitative mitochondria-focused proteomics (label-free), mitochondrial respiration assays, immunofluorescence for mitophagy markers, validation in patient fibroblasts Cell death discovery Medium 32257390
2019 CLN5 deficiency causes elevated basal LC3-II levels and increased autophagic flux in patient fibroblasts and CLN5-knockdown HeLa cells. Alpha-synuclein (α-syn) gene SNCA is highly upregulated at mRNA and protein levels in CLN5-deficient cells, and α-syn localizes near lysosomes. Knockdown of SNCA reversed lysosomal perinuclear clustering caused by CLN5 deficiency. Western blotting (LC3-II), tandem fluorescent mRFP-GFP-LC3 autophagy flux assay, qPCR for SNCA, immunofluorescence for α-syn localization, SNCA siRNA rescue experiment Scientific reports Medium 30655561
2024 In Dictyostelium, Cln5 is released from cells via signal-peptide-mediated secretion and through pathways linked to autophagy. Release requires autophagy proteins Atg1, Atg5, and Atg9, as well as autophagosomal-lysosomal fusion. Release also requires microfilaments and Dictyostelium homologs of AP-3, LYST, mucopilin-1, and WASH (regulators of lysosomal exocytosis). Cln5 release is regulated by the amount of extracellular CtsD (cathepsin D). Genetic knockouts of autophagy genes, cytoskeleton inhibitor experiments, secretion assays with Western blotting and mass spectrometry in Dictyostelium Traffic (Copenhagen, Denmark) Medium 38272448
2009 In wild-type CLN5 mutant cells (CLN5 p.Trp379Cys and p.Leu358AlafsX4), both mutant CLN5 proteins are retained in the endoplasmic reticulum rather than reaching the lysosome, as demonstrated by double immunofluorescence microscopy. The truncation mutant lacks an N-glycosylation site at Asn401. Double immunofluorescence microscopy, expression analysis, Western blotting in patient-derived cell lines Human mutation Medium 19309691
2004 Mouse Cln5 is a soluble lysosomal glycoprotein. In situ hybridization and immunohistochemistry showed prominent expression in cerebellar Purkinje cells, cerebral neurons, hippocampal pyramidal cells, and interneurons, with expression beginning at E15 and increasing through development. In situ hybridization, immunohistochemistry, in vitro expression in COS-1, HeLa, and neuronal cells Neurobiology of disease Medium 15207259
2012 CLN5-deficient fibroblasts show decreased levels of ceramide, sphingomyelin, and glycosphingolipids, and reduced ceramide synthase activity. CLN8 protein expression can correct growth and apoptosis defects in CLN5-deficient cells. Comparison by Co-IP and differential gel electrophoresis revealed absence of γ-actin in the CerS1-bound protein complex in CLN5-deficient cells. Co-immunoprecipitation, differential gel electrophoresis, mass spectrometry, ceramide species measurement by MS, cell viability and apoptosis assays Electrophoresis Medium 23160995

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proceedings of the National Academy of Sciences of the United States of America 554 19174516
1998 CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis. Nature genetics 225 9662406
2002 Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein. Human molecular genetics 101 11971870
2002 Neuronal ceroid lipofuscinoses are connected at molecular level: interaction of CLN5 protein with CLN2 and CLN3. Molecular biology of the cell 91 12134079
2005 A mutation in canine CLN5 causes neuronal ceroid lipofuscinosis in Border collie dogs. Genomics 76 16033706
2004 A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging. Human molecular genetics 72 15459177
2009 Novel interactions of CLN5 support molecular networking between Neuronal Ceroid Lipofuscinosis proteins. BMC cell biology 69 19941651
2012 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. Molecular and cellular biology 68 22431521
2000 Phenotype-genotype correlation in eight patients with Finnish variant late infantile NCL (CLN5). Neurology 62 10953198
2007 A new large animal model of CLN5 neuronal ceroid lipofuscinosis in Borderdale sheep is caused by a nucleotide substitution at a consensus splice site (c.571+1G>A) leading to excision of exon 3. Neurobiology of disease 60 17988881
2010 CLN5 mutations are frequent in juvenile and late-onset non-Finnish patients with NCL. Neurology 59 20157158
1996 The age of human mutation: genealogical and linkage disequilibrium analysis of the CLN5 mutation in the Finnish population. American journal of human genetics 59 8644710
2023 The Batten disease gene product CLN5 is the lysosomal bis(monoacylglycero)phosphate synthase. Science (New York, N.Y.) 58 37708259
2018 Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease. Molecular therapy : the journal of the American Society of Gene Therapy 55 30078766
2004 The mouse ortholog of the neuronal ceroid lipofuscinosis CLN5 gene encodes a soluble lysosomal glycoprotein expressed in the developing brain. Neurobiology of disease 53 15207259
2017 Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy. Scientific reports 52 28487519
2013 The role of N-glycosylation in folding, trafficking, and functionality of lysosomal protein CLN5. PloS one 52 24058541
1999 Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. Human mutation 50 10477428
2017 Cln5 is secreted and functions as a glycoside hydrolase in Dictyostelium. Cellular signalling 46 29128403
2012 CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches. Electrophoresis 46 23160995
2011 Cln5-deficiency in mice leads to microglial activation, defective myelination and changes in lipid metabolism. Neurobiology of disease 44 22182690
1996 Efficient construction of a physical map by fiber-FISH of the CLN5 region: refined assignment and long-range contig covering the critical region on 13q22. Genomics 44 8661106
2015 Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Molecular genetics and metabolism 42 25934231
2005 A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset. Neurology 41 15728307
2018 An Alzheimer's Disease-Linked Loss-of-Function CLN5 Variant Impairs Cathepsin D Maturation, Consistent with a Retromer Trafficking Defect. Molecular and cellular biology 40 30037983
2009 Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibship. Human mutation 40 19309691
2010 The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular maturation, transport, and consequences of mutations. Human mutation 38 20052765
2009 Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL. Neurobiology of disease 38 19385065
2016 Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies. Journal of veterinary internal medicine 36 27203721
2013 Inhibition of storage pathology in prenatal CLN5-deficient sheep neural cultures by lentiviral gene therapy. Neurobiology of disease 35 24269732
2007 Revelation of a novel CLN5 mutation in early juvenile neuronal ceroid lipofuscinosis. Neuropediatrics 35 17607606
2019 Autophagy-lysosome pathway alterations and alpha-synuclein up-regulation in the subtype of neuronal ceroid lipofuscinosis, CLN5 disease. Scientific reports 34 30655561
2014 Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations. Journal of neurology 31 25359263
2020 Proteomic and functional analyses in disease models reveal CLN5 protein involvement in mitochondrial dysfunction. Cell death discovery 28 32257390
2006 Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency. Molecular genetics and metabolism 28 16814585
2006 Neuronal ceroid lipofuscinosis in Devon cattle is caused by a single base duplication (c.662dupG) in the bovine CLN5 gene. Biochimica et biophysica acta 28 16935476
2021 Intravitreal gene therapy protects against retinal dysfunction and degeneration in sheep with CLN5 Batten disease. Experimental eye research 27 33930398
2017 Characterisation of early changes in ovine CLN5 and CLN6 Batten disease neural cultures for the rapid screening of therapeutics. Neurobiology of disease 27 28065762
2017 Induced Pluripotent Stem Cells Derived from a CLN5 Patient Manifest Phenotypic Characteristics of Neuronal Ceroid Lipofuscinoses. International journal of molecular sciences 27 28468312
2015 Molecular neuropathology of the synapse in sheep with CLN5 Batten disease. Brain and behavior 27 26664787
2000 CLN-1 and CLN-5, genes for infantile and variant late infantile neuronal ceroid lipofuscinoses, are expressed in the embryonic human brain. The Journal of comparative neurology 27 10992246
2022 Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration. Science advances 26 35427157
2021 CLN5 and CLN3 function as a complex to regulate endolysosome function. The Biochemical journal 26 34060589
2018 Secretion and function of Cln5 during the early stages of Dictyostelium development. Biochimica et biophysica acta. Molecular cell research 26 30048658
2017 CLN5 is cleaved by members of the SPP/SPPL family to produce a mature soluble protein. Experimental cell research 26 28442266
2021 A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis. Cellular and molecular life sciences : CMLS 24 33792748
2016 An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 27488642
2022 KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses. Science advances 22 35921411
2021 Deficiency of the Lysosomal Protein CLN5 Alters Lysosomal Function and Movement. Biomolecules 21 34680045
2017 Loss of Cln5 causes altered neurogenesis in a mouse model of a childhood neurodegenerative disorder. Disease models & mechanisms 19 28733362
2014 Neuronal ceroid lipofuscinosis genes, CLN2, CLN3 and CLN5 are spatially and temporally co-expressed in a developing mouse brain. Experimental and molecular pathology 19 25303899
2015 Proteolytic processing of the neuronal ceroid lipofuscinosis related lysosomal protein CLN5. Experimental cell research 18 26342652
2021 Aberrant Autophagy Impacts Growth and Multicellular Development in a Dictyostelium Knockout Model of CLN5 Disease. Frontiers in cell and developmental biology 17 34291044
2020 Mfsd8 localizes to endocytic compartments and influences the secretion of Cln5 and cathepsin D in Dictyostelium. Cellular signalling 17 32087303
2013 Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5. Human mutation 16 24038957
2001 Studies of homogenous populations: CLN5 and CLN8. Advances in genetics 15 11332769
2022 Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease. Cells 14 35681535
2019 A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs. Molecular genetics and metabolism 14 31101435
2019 Loss of Cln5 leads to altered Gad1 expression and deficits in interneuron development in mice. Human molecular genetics 14 31294445
1999 Prenatal diagnosis of variant late infantile neuronal ceroid lipofuscinosis (vLINCL[Finnish]; CLN5). Prenatal diagnosis 13 10419622
1994 A variant form of late infantile neuronal ceroid lipofuscinosis (CLN5) is not an allelic form of Batten (Spielmeyer-Vogt-Sjögren, CLN3) disease: exclusion of linkage to the CLN3 region of chromosome 16. Genomics 11 8020979
2024 Mechanisms regulating the intracellular trafficking and release of CLN5 and CTSD. Traffic (Copenhagen, Denmark) 9 38272448
2023 Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease). Developmental neurobiology 9 37246363
2023 Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease. Frontiers in genetics 9 37614821
2023 Efficacy of dual intracerebroventricular and intravitreal CLN5 gene therapy in sheep prompts the first clinical trial to treat CLN5 Batten disease. Frontiers in pharmacology 9 37942487
2022 Lysosomal dysfunction, autophagic defects, and CLN5 accumulation underlie the pathogenesis of KCTD7-mutated neuronal ceroid lipofuscinoses. Autophagy 9 36368077
2023 Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis. Brain communications 8 36632184
2021 Association of the Recurrent Rare Variant c.415T>C p.Phe139Leu in CLN5 With a Recessively Inherited Macular Dystrophy. JAMA ophthalmology 8 33507209
2020 Novel likely disease-causing CLN5 variants identified in Pakistani patients with neuronal ceroid lipofuscinosis. Journal of the neurological sciences 8 32302805
2020 Functional Analysis of a Novel CLN5 Mutation Identified in a Patient With Neuronal Ceroid Lipofuscinosis. Frontiers in genetics 8 32983231
2021 Electroretinography data from ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses. Data in brief 7 34141843
1999 Positional cloning of the CLN5 gene defective in the Finnish variant of the LINCL. Molecular genetics and metabolism 7 10191122
2023 Mechanistic Insights into S-Depalmitolyse Activity of Cln5 Protein Linked to Neurodegeneration and Batten Disease: A QM/MM Study. Journal of the American Chemical Society 6 38055807
2022 HAGLROS knockdown restrained cell proliferation, migration and invasion and facilitated apoptosis in laryngeal cancer via miR-138-5p/CLN5 axis. Journal of clinical laboratory analysis 6 36347825
2019 The Neuronal Ceroid Lipofuscinoses-Linked Loss of Function CLN5 and CLN8 Variants Disrupt Normal Lysosomal Function. Neuromolecular medicine 6 30919163
2018 Novel Mutations in CLN5 of Chinese Patients With Neuronal Ceroid Lipofuscinosis. Journal of child neurology 6 30264640
2021 Knockdown of CLN5 inhibits the tumorigenic properties of glioblastoma cells via the Akt/mTOR signaling pathway. Oncology letters 5 33777210
2020 CLN5 in heterozygosis may protect against the development of tumors in a VHL patient. Orphanet journal of rare diseases 5 32487141
2025 CLN5 deficiency impairs glucose uptake and uncovers PHGDH as a potential biomarker in Batten disease. Molecular psychiatry 4 40346285
2012 [Neuronal ceroid lipofuscinosis: diagnostic algorithm and clinical description of the Finnish (CLN5) and Turkish (CLN7) variants late infantile]. Revista de neurologia 4 22532218
2022 An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum. Frontiers in genetics 3 36437924
1999 Transcript identification on the CLN5 region on chromosome 13q22. Human genetics 3 10480355
2023 Characterization of two human induced pluripotent stem cell lines derived from Batten disease patient fibroblasts harbouring CLN5 mutations. Stem cell research 2 38141358
2026 Brain-Directed AAV Gene Therapy Rescues a Mouse Model of the CLN5 Form of Neuronal Ceroid Lipofuscinosis Disease and Normalizes a Blood Plasma Biomarker of Neurodegeneration. Human gene therapy 1 41457644
2025 Magnetic Resonance Imaging as a Readout of CLN5 Gene Therapy Efficacy in Sheep. Brain and behavior 1 40181626
2024 Drug-refractory epilepsy due to a novel CLN5 mutation: A report of three patients from an Indian family. Seizure 1 39667065
2021 A novel CLN5 mutation in Turkish patient with variant late-onset neuronal ceroid lipofuscinosis and recurrent fractures that causes severe morbidity. Neurocase 1 34678132
2026 CLN5 disease-causing mutations impact lysosomal biology by affecting intracellular degradation and protein trafficking. Biochimica et biophysica acta. Molecular basis of disease 0 42031177
2025 Genomic insights into autosomal recessive epilepsy: novel pathogenic variants in ITPA and CLN5 identified in consanguineous families. Molecular biology reports 0 41003830

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