Affinage

CTSD

Cathepsin D · UniProt P07339

Length
412 aa
Mass
44.6 kDa
Annotated
2026-06-09
49 papers in source corpus 19 papers cited in narrative 21 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

CTSD (cathepsin D) is a lysosomal aspartic protease that maintains neuronal and cellular proteostasis and autophagic flux by degrading substrates in the lysosome (PMID:32450052, PMID:35287553). It is synthesized as an inactive pro-enzyme that is matured to its catalytically active form, and this maturation is the decisive step controlling its function: missense mutations that specifically reduce catalytic activity (Met199Ile; Ser100Phe) — without altering protein stability or other lysosomal enzyme activities — cause neuronal ceroid lipofuscinosis (CLN10), establishing that enzymatic activity, not protein abundance, is required to prevent lysosomal storage pathology (PMID:16386934, PMID:18762956). Mature CTSD sustains autophagy by enabling autophagosome–lysosome fusion, and its loss causes lysosomal dysfunction and impaired autophagic degradation (PMID:32450052, PMID:32253787). Among its substrates, CTSD is the major lysosomal protease degrading SNCA/α-synuclein, and recombinant pro-CTSD delivered via mannose-6-phosphate receptor-mediated endocytosis is correctly trafficked to lysosomes, matured, and restores defective proteolysis and autophagic flux in CTSD-deficient disease models, reducing insoluble α-synuclein conformers in patient-derived neurons and ctsd-deficient mouse brains (PMID:31282275, PMID:35287553). Its maturation and trafficking are governed by post-translational modifications — N-glycosylation (controlling secretion of pro-CTSD versus intracellular retention, and protease activity), O-GlcNAcylation, and H2S-dependent S-sulfhydration of pro-CTSD — which collectively partition CTSD between an intracellular pro-apoptotic/proteostatic role and a secreted extracellular pool (PMID:32324083, PMID:39716927, PMID:37442287, PMID:41558604). CTSD transcription is induced by estrogen receptor alpha through chromatin looping to a distal enhancer 9 kb upstream of its start site (PMID:19383337), and it is suppressed downstream of an mTOR–MITF axis in macrophages (PMID:40886983). Beyond the lysosome, secreted or circulatory pro-CTSD acts in trans: it binds the Cluster II domain of endothelial LRP1 to trigger LRP1 lysosomal degradation and impair brain Aβ clearance (PMID:42162956), and engages LRP6 to mediate degradation of HSP90α in cardiomyocytes (PMID:39779966). Loss of CTSD enzymatic activity causes CLN10/neuronal ceroid lipofuscinosis (PMID:16386934, PMID:18762956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Established that it is CTSD catalytic activity specifically — not general lysosomal enzyme deficiency — that prevents neuronal ceroid lipofuscinosis, defining CTSD as a disease gene through its enzymatic function.

    Evidence Enzyme-specific activity assays comparing CTSD to 15 other lysosomal enzymes plus genetic linkage in Met199Ile American Bulldogs

    PMID:16386934

    Open questions at the time
    • Did not identify the physiological substrates whose accumulation drives NCL pathology
    • Canine model; human variant spectrum addressed separately
  2. 2008 Medium

    Distinguished catalytic activity from protein stability as the critical determinant, showing a stable, normally processed CTSD protein with marginal activity still causes congenital CLN10.

    Evidence Enzymatic activity assay and processing/stability analysis in patient fibroblasts carrying p.Ser100Phe, with overexpression studies

    PMID:18762956

    Open questions at the time
    • Mechanism linking marginal activity to congenital lethality not resolved
    • Single patient genotype
  3. 2008 Medium

    Defined how CTSD is transcriptionally controlled, identifying ERα-driven induction via long-range chromatin looping to a distal enhancer.

    Evidence ChIP for ERα and phospho-Pol II, bisulfite sequencing, and chromatin looping assays in MCF-7 cells

    PMID:19383337

    Open questions at the time
    • Functional consequence of transient CpG methylation not established
    • Restricted to one breast cancer cell line
  4. 2020 Medium

    Resolved the localization-versus-function switch, showing autophagy drives intracellular CTSD maturation toward apoptosis while N233 glycosylation routes pro-CTSD to secretion for proliferative signaling.

    Evidence RNAi, autophagy modulation, PNGase F glycosylation assay, and caspase-3 activity in an insect (Helicoverpa armigera) model

    PMID:32324083

    Open questions at the time
    • Demonstrated in an insect model; mammalian generality not shown here
    • Glycosite numbering and mechanism differ across mammalian studies
  5. 2020 Medium

    Established CTSD as causally required for neuronal lysosomal homeostasis and autophagic flux, with knockdown sufficient to cause dysfunction and rescue restoring viability.

    Evidence shRNA knockdown plus lentiviral rescue with lysosomal and cell-death assays in mouse cortical neurons and an MCAO stroke model; siRNA/pepstatin A blocking autophagosome-lysosome fusion in glioblastoma

    PMID:32253787 PMID:32450052

    Open questions at the time
    • Direct molecular step at which CTSD enables fusion not defined
    • Substrate(s) mediating the fusion phenotype unidentified
  6. 2022 High

    Identified α-synuclein as a key CTSD substrate and demonstrated therapeutic enzyme reconstitution, showing recombinant pro-CTSD reduces insoluble SNCA in human and murine neuronal models.

    Evidence rHsCTSD uptake/lysosomal targeting, SNCA solubility fractionation, A53T PD iPSC neurons, ctsd-knockout mice; earlier CLN10 reconstitution work established M6P-receptor uptake and autophagy rescue

    PMID:31282275 PMID:35287553

    Open questions at the time
    • Cleavage sites and kinetics on SNCA not fully mapped
    • Long-term in vivo efficacy and delivery not addressed
  7. 2024 Medium

    Defined N-glycosylation as a regulator of CTSD protease activity and downstream substrate processing, linking glycosylated CTSD to ACADM cleavage and ferroptosis-related signaling in cancer.

    Evidence N-glycoproteomics, N263 site-directed mutagenesis, DDOST/STT3B manipulation, and ferroptosis-marker assays in colorectal cancer cells

    PMID:39716927

    Open questions at the time
    • Relationship between distinct reported glycosites (N233/N258/N263) unresolved
    • Single cancer-cell context
  8. 2023 Medium

    Extended PTM control of CTSD maturation to O-GlcNAcylation, showing reduced O-GlcNAcylation impairs maturation and autophagic degradation.

    Evidence IP, mature/pro CTSD Western blots, and OGT/OGA inhibitor (OSMI/TMG) modulation with lysosomal function assays

    PMID:37442287

    Open questions at the time
    • Direct O-GlcNAc site on CTSD not mapped
    • Whether effect is direct or via trafficking machinery unclear
  9. 2023 Medium

    Placed CTSD downstream of microRNA and epigenetic control, showing GR/H3K9ac-driven miR-1912-3p suppresses CTSD to inhibit chondrocyte autophagic flux, reversible by CTSD overexpression.

    Evidence miR target validation, H3K9ac ChIP, CTSD overexpression rescue, and autophagic flux assays in vitro and in a PDE rat model; complementary miR-214-3p targeting validated in porcine intestinal epithelial cells

    PMID:37249374 PMID:42117833

    Open questions at the time
    • Physiological contexts where each miRNA dominates not defined
    • miR-214-3p evidence is Low-confidence, non-human
  10. 2025 Medium

    Connected CTSD to upstream signaling controlling its expression, placing it downstream of an mTOR-MITF axis in macrophage lysosomal homeostasis.

    Evidence Myeloid-specific SAMHD1-KO mice, scRNA-seq, rapamycin treatment, and MITF nuclear translocation/CTSD expression assays

    PMID:40886983

    Open questions at the time
    • Whether MITF binds the CTSD locus directly not shown
    • Single disease context
  11. 2025 Medium

    Identified an extracellular/trans CTSD function in cardiomyocytes, where LRP6 facilitates CTSD-mediated HSP90α degradation to limit β-catenin-driven hypertrophy.

    Evidence MS co-IP, cardiomyocyte LRP6 overexpression mice, TAC model, pepstatin A inhibition, and recombinant HSP90α rescue

    PMID:39779966

    Open questions at the time
    • Direct CTSD cleavage of HSP90α versus indirect effect not fully separated
    • Subcellular compartment of the degradation event unclear
  12. 2026 Medium

    Established H2S-dependent S-sulfhydration of pro-CTSD as a maturation brake, with loss of sulfhydration promoting active CTSD that drives PANoptosis after TBI.

    Evidence AAV-shSnapin knockdown, Snapin-CBS co-IP, biotin switch S-sulfhydration assay, H2S measurement, and pepstatin A/NaHS rescue with behavioral tests

    PMID:41558604

    Open questions at the time
    • Sulfhydrated cysteine residue on pro-CTSD not mapped
    • Single injury model
  13. 2026 Medium

    Defined a pathogenic trans action of circulatory pro-CTSD, showing it binds the LRP1 Cluster II domain to trigger LRP1 degradation and impair brain Aβ clearance.

    Evidence Western blot, domain-specific binding assay, transgenic mice with high circulatory pro-CTSD, and confocal/TIRF imaging of internalization in Alzheimer's models

    PMID:42162956

    Open questions at the time
    • Whether pro-CTSD enzymatic activity is required for LRP1 degradation not resolved
    • Source of elevated circulatory pro-CTSD in disease unclear
  14. 2026 Medium

    Linked macrophage CTSD secretion to a glycosylation-trafficking circuit, showing KIF13B loss stabilizes STT3A to enhance CTSD glycosylation and secretion, promoting hepatocyte lipid accumulation via THBS1.

    Evidence Myeloid-specific Kif13b-KO mice, MASLD model, STT3A degradation assays, and CTSD-THBS1 interaction analysis

    PMID:41746601

    Open questions at the time
    • Whether CTSD acts as protease or ligand on hepatocytes not separated
    • Direct CTSD-THBS1 binding interface not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct N-glycosites (N233/N258/N263), O-GlcNAcylation, and S-sulfhydration are integrated to set the balance between intracellular maturation, secretion, and substrate selectivity remains unresolved.
  • No unified model reconciling the multiple reported glycosites and PTMs
  • Structural basis of pro-CTSD maturation control not defined
  • Quantitative partitioning between lysosomal and secreted pools across cell types unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 3 GO:0005764 lysosome 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 3
Partners
ACADMHSP90A1LRP1LRP6SNCASTT3ATHBS1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Autophagy triggers CTSD maturation and localization inside cells to promote apoptosis. Glycosylation of asparagine 233 (N233) determines pro-CTSD secretion outside cells (for proliferative signaling), while autophagy-mediated maturation retains CTSD inside cells where it activates caspase-3 and promotes apoptosis, establishing a dual-function regulatory mechanism. RNAi knockdown, pharmacological autophagy modulation, PNGase F glycosylation assay, immunofluorescence localization, caspase-3 activity assay in Helicoverpa armigera model Autophagy Medium 32324083
2020 CTSD is an essential lysosomal protease in neurons; shRNA-mediated knockdown of CTSD alone is sufficient to cause lysosomal dysfunction, and lentiviral restoration of CTSD activity rescues lysosomal function and cell viability in oxygen-glucose deprivation (OGD) conditions, establishing a direct causal role for CTSD in maintaining neuronal lysosomal homeostasis. shRNA knockdown, lentiviral transduction, lysosomal function assays, cell death assays in mouse cortical neurons and MCAO stroke model Autophagy Medium 32450052
2006 A missense mutation (Met199Ile) in CTSD reduces cathepsin D-specific enzymatic activity to 36% of normal in affected American Bulldogs while leaving 15 other lysosomal enzyme activities unchanged, causing neuronal ceroid lipofuscinosis (NCL), establishing that CTSD enzymatic activity is specifically required for preventing NCL pathology. Enzymatic activity assays for cathepsin D and 15 other lysosomal enzymes, genetic linkage analysis, histopathology Molecular genetics and metabolism High 16386934
2019 Recombinant human pro-CTSD is taken up by cells via mannose-6-phosphate receptor-mediated endocytosis, correctly targeted to lysosomes, and processed to the active mature form, where it corrects defective proteolysis and restores autophagic flux in CTSD-deficient CLN10 disease models in vitro and in vivo. Recombinant protein uptake assays, lysosomal targeting by immunofluorescence/fractionation, enzymatic activity assay, autophagic flux measurement, murine CLN10 model in vivo dosing Autophagy High 31282275
2022 CTSD is the major lysosomal protease responsible for SNCA/α-synuclein degradation; recombinant human pro-CTSD is endocytosed by neuronal cells, trafficked to lysosomes, matured to active enzyme, and reduces insoluble SNCA conformers in PD patient-derived iPSC dopaminergic neurons and in ctsd-deficient mouse brains. rHsCTSD uptake and lysosomal targeting assays, SNCA solubility fractionation (Triton-soluble/insoluble), iPSC-derived neurons from A53T SNCA PD patients, ctsd-knockout mouse model, structured illumination microscopy Autophagy High 35287553
2008 Estrogen receptor alpha (ERα) up-regulates CTSD expression through a distal enhancer element located 9 kb upstream of the CTSD transcription start site via a chromatin looping mechanism, with ERα and phosphorylated RNA Pol II recruited to this distal ERE, and transient CpG methylation occurring at both the proximal promoter and the distal enhancer upon estrogen stimulation. Chromatin immunoprecipitation (ChIP) for ERα and phospho-Pol II, bisulfite sequencing for CpG methylation kinetics, chromosome conformation capture or looping assay in MCF-7 cells Molecular oncology Medium 19383337
2020 CTSD inhibition (siRNA or pepstatin A) attenuates autophagy by blocking autophagosome-lysosome fusion, resulting in increased autophagosomes and decreased autolysosomes, and this impaired autophagy increases radiosensitivity of glioblastoma cells. CTSD expression positively correlates with the autophagy marker LC3-II/I and negatively with p62 after ionizing radiation. siRNA knockdown, pepstatin A inhibition, Western blot, immunofluorescence for autophagosome/autolysosome quantification in radioresistant GBM cells Molecular carcinogenesis Medium 32253787
2024 N-glycosylation of CTSD at residue N263, regulated by the glycosyltransferase complex DDOST/STT3B, affects CTSD protease activity; glycosylated CTSD cleaves ACADM, and ACADM in turn regulates ferroptosis-related proteins (ACSL4, SLC7A11, GPX4) to influence invasion and metastasis of colorectal cancer cells. N-glycoproteomics, site-directed mutagenesis (N263), DDOST/STT3B manipulation, ACADM substrate identification, ferroptosis marker (ACSL4/SLC7A11/GPX4) quantification, invasion/metastasis assays Advanced science Medium 39716927
2023 Swainsonine reduces O-GlcNAcylation of CTSD, which impairs CTSD maturation (reducing mature CTSD levels), leading to lysosomal dysfunction and inhibition of autophagy degradation; pharmacological increase of O-GlcNAcylation (with TMG) promotes autophagy while decrease (with OSMI) inhibits it, implicating O-GlcNAcylation as a post-translational modification that regulates CTSD maturation. Immunoprecipitation, Western blot for mature/pro CTSD forms, OGA inhibitor (TMG) and OGT inhibitor (OSMI) treatments, proteomics, lysosomal function assays Chemico-biological interactions Medium 37442287
2024 CLN5 release from Dictyostelium discoideum cells is regulated by extracellular CtsD levels; autophagy induction promotes release of both Cln5 and CtsD; release requires signal peptides, autophagy proteins (Atg1, Atg5, Atg9 for Cln5; Atg1 and Atg5 for CtsD), autophagosomal-lysosomal fusion, microfilaments, and lysosomal exocytosis components (AP-3, LYST, mucopilin-1, WASH); sortilin and cation-independent mannose-6-phosphate receptor homologs regulate intracellular/extracellular distribution of CtsD. Genetic knockouts of autophagy and trafficking genes in Dictyostelium, secretion assays, glycosylation analysis, pharmacological autophagy induction Traffic Medium 38272448
2025 LRP6 interacts with HSP90α and CTSD in cardiomyocytes under mechanical stress; LRP6 facilitates CTSD-mediated degradation of HSP90α, which consequently inhibits β-catenin activation and reduces cardiac hypertrophy; pepstatin A (CTSD inhibitor) partly abolishes the cardioprotective effect of LRP6 overexpression, establishing CTSD as a downstream effector in the LRP6/CTSD/HSP90α/β-catenin axis. Mass spectrometry co-immunoprecipitation, cardiomyocyte-specific LRP6 overexpression mice, TAC model, pepstatin A pharmacological inhibition, recombinant HSP90α rescue, echocardiography Acta pharmacologica Sinica Medium 39779966
2025 SAMHD1 deficiency impairs lysosomal function in macrophages by enhancing MITF nuclear translocation, which suppresses CTSD expression; pharmacological inhibition of PI3K/AKT/mTOR restores MITF-CTSD signaling and lysosomal function, placing CTSD downstream of the mTOR-MITF axis in macrophage autophagy-lysosomal homeostasis. Myeloid-specific SAMHD1-KO mice, scRNA-seq, mTOR pathway inhibition (rapamycin), MITF nuclear translocation assay, CTSD expression and lysosomal flux measurements International journal of biological macromolecules Medium 40886983
2026 Snapin binds cystathionine β-synthase (CBS) in neurons after mild TBI, disrupting H2S metabolic homeostasis and reducing endogenous H2S levels; decreased H2S limits S-sulfhydration of pro-CTSD, promoting its maturation into active CTSD which induces PANoptosis; both pepstatin A (CTSD inhibitor) and NaHS (H2S donor) are neuroprotective, establishing that H2S-dependent S-sulfhydration of pro-CTSD is a post-translational modification that regulates CTSD maturation. AAV-shSnapin conditional knockdown, co-immunoprecipitation (Snapin-CBS interaction), modified biotin switch assay for S-sulfhydration of CTSD, endogenous H2S measurement by sulfide ion-selective electrode, pepstatin A and NaHS treatment, behavioral tests Journal of advanced research Medium 41558604
2026 Circulatory pro-CTSD binds the Cluster II domain of LRP1 on brain endothelial cells, triggering LRP1 endocytosis and lysosomal degradation, which reduces endothelial LRP1 levels and impairs brain-to-blood Aβ clearance in Alzheimer's disease mouse models. Western blot for LRP1 in pro-CTSD-treated brain endothelial cells, transgenic mice with high circulatory pro-CTSD, confocal and TIRF microscopy for pro-CTSD internalization and LRP1 co-localization, immunostaining for Aβ deposition, Cluster II domain binding specificity assay Alzheimer's & dementia Medium 42162956
2026 In macrophages, KIF13B deficiency impairs proteasome-dependent degradation of the glycosyltransferase STT3A, thereby enhancing CTSD glycosylation and secretion, which promotes lipid accumulation and inflammatory responses in hepatocytes through interaction with the hepatocyte membrane protein THBS1, establishing the STT3A/CTSD glycosylation/secretion axis as downstream of KIF13B. Myeloid-specific Kif13b KO mice, diet-induced MASLD model, STT3A degradation assay, CTSD glycosylation and secretion measurements, CTSD-THBS1 interaction analysis, ZNF384 transcription factor binding to KIF13B promoter Hepatology Medium 41746601
2008 A novel CTSD missense mutation (c.299C>T, p.Ser100Phe) reduces cathepsin D enzymatic activity to marginal levels in patient fibroblasts while the protein remains stable and normally processed, causing congenital neuronal ceroid lipofuscinosis (CLN10), confirming that catalytic activity rather than protein stability is critical for CTSD function. Cathepsin D enzymatic activity assay in patient fibroblasts, overexpression studies, protein stability and processing analysis Acta neuropathologica Medium 18762956
2023 miR-1912-3p directly targets CTSD in fetal chondrocytes; dexamethasone activates glucocorticoid receptor (GR) to increase H3K9ac and miR-1912-3p expression, which suppresses CTSD expression and inhibits autophagic flux; overexpression of CTSD rescues autophagic flux inhibited by dexamethasone, placing CTSD downstream of the GR/H3K9ac/miR-1912-3p axis in chondrocyte autophagy regulation. CTSD overexpression rescue experiments, miR-1912-3p target validation, H3K9ac ChIP, GR pathway inhibition, autophagic flux assays (autolysosome accumulation), in vivo PDE rat model FASEB journal Medium 37249374
2025 Cathepsin D (CtsD) in astrocytes cleaves α-synuclein pre-formed fibrils (PFFs) into C-terminally truncated, seeding-competent species; these truncated species are transferred to neurons where they promote Lewy neurite-like aggregate growth. α-syn PFF exposure disrupts lysosomal membrane integrity in astrocytes, leading to CtsD upregulation in a feed-forward mechanism. Neuron-astrocyte co-culture system, lysosomal protease identification (CtsD), α-syn PFF truncation assay, aggregate seeding assay in neurons, lysosomal membrane integrity assessment bioRxivpreprint Low
2025 CtsD deletion in mice dramatically decreases bone mass with decreased osteoblast number/activity and increased osteoclast number/activity; siRNA-mediated CTSD inactivation in osteoblasts (MC3T3E1) attenuates osteoblastic differentiation and decreases LC3B and P62 expression, while inactivation in osteoclasts (RAW264.7) increases osteoclast differentiation with decreased LC3B but upregulated P62, demonstrating that CTSD mediates autophagy through distinct mechanisms in osteoblasts versus osteoclasts. CtsD conditional KO mice, microCT, histomorphometry, siRNA knockdown in MC3T3E1 and RAW264.7 cells, LC3B and P62 expression, differentiation assays bioRxivpreprint Low
2026 miR-214-3p directly targets CTSD (validated by luciferase assay); overexpression of CTSD reverses the protective effects of miR-214-3p mimic on lysosomal acidification and LAMP1 levels in porcine intestinal epithelial cells, establishing CTSD as a direct functional target of miR-214-3p in regulating lysosomal homeostasis. Luciferase reporter assay for miR-214-3p/CTSD interaction, CTSD overexpression rescue, lysosomal acidification measurement, LAMP1 expression, cell viability assays in IPEC-J2 cells Biology Low 42117833
2024 N-glycosylation of CTSD at residue N258 (CTSD-N258A mutant) promotes lysosomal localization of CTSD and affects lysosomal membrane permeability and apoptosis in BMSCs; the N258A mutant reduces CTSD levels in cytoplasm and lysosomes and inhibits BMSC apoptosis in a dexamethasone-induced model. CTSD N258A site-directed mutagenesis, flow cytometry for apoptosis, confocal microscopy for lysosomal colocalization, AO staining for lysosomal membrane permeability, Western blot for apoptosis-related proteins PloS one Low 41931502

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in streptococcus pneumoniae. Molecular microbiology 178 10760144
2020 Autophagy triggers CTSD (cathepsin D) maturation and localization inside cells to promote apoptosis. Autophagy 131 32324083
2003 Positive correlation between tyrosine phosphorylation of CpsD and capsular polysaccharide production in Streptococcus pneumoniae. Journal of bacteriology 117 14526017
2004 The effect that mutations in the conserved capsular polysaccharide biosynthesis genes cpsA, cpsB, and cpsD have on virulence of Streptococcus pneumoniae. The Journal of infectious diseases 107 15122528
1993 Identification of cpsD, a gene essential for type III capsule expression in group B streptococci. Molecular microbiology 106 8355611
2020 Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective. Autophagy 105 32450052
2006 A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Molecular genetics and metabolism 104 16386934
2019 Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis. Autophagy 83 31282275
2003 Mutational analysis of the carboxy-terminal (YGX)4 repeat domain of CpsD, an autophosphorylating tyrosine kinase required for capsule biosynthesis in Streptococcus pneumoniae. Journal of bacteriology 70 12730159
2022 Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models. Autophagy 67 35287553
2008 Novel mutation and the first prenatal screening of cathepsin D deficiency (CLN10). Acta neuropathologica 55 18762956
2015 Autophosphorylation of the Bacterial Tyrosine-Kinase CpsD Connects Capsule Synthesis with the Cell Cycle in Streptococcus pneumoniae. PLoS genetics 53 26378458
2020 Inhibition of Cathepsin D (CTSD) enhances radiosensitivity of glioblastoma cells by attenuating autophagy. Molecular carcinogenesis 45 32253787
2023 TMT-based quantitative proteomics revealed protective efficacy of Icariside II against airway inflammation and remodeling via inhibiting LAMP2, CTSD and CTSS expression in OVA-induced chronic asthma mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 43 37451150
2008 E2-mediated cathepsin D (CTSD) activation involves looping of distal enhancer elements. Molecular oncology 36 19383337
1999 Analysis of the 5' portion of the type 19A capsule locus identifies two classes of cpsC, cpsD, and cpsE genes in Streptococcus pneumoniae. Journal of bacteriology 35 10348877
2010 The insulin-like growth factor 2 (IGF2) gene intron3-g.3072G>A polymorphism is not the only Sus scrofa chromosome 2p mutation affecting meat production and carcass traits in pigs: evidence from the effects of a cathepsin D (CTSD) gene polymorphism. Journal of animal science 30 20382874
2006 Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease. Journal of the neurological sciences 29 16784755
2001 No evidence for genetic association or linkage of the cathepsin D (CTSD) exon 2 polymorphism and Alzheimer disease. Annals of neurology 27 11198280
2007 Rapid detection and identification of the bacterium Pantoea stewartii in maize by TaqMan real-time PCR assay targeting the cpsD gene. Journal of applied microbiology 24 18179542
2019 Anxa2- and Ctsd-knockout CHO cell lines to diminish the risk of contamination with host cell proteins. Biotechnology progress 23 30972970
2021 Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death. BMC cardiovascular disorders 18 33964876
2020 Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non-Small Cell Lung Cancer Through Inactivating ERK/CTSD Signalling Pathways. Molecules (Basel, Switzerland) 18 32244796
2006 Isolation, activity and immunological characterisation of a secreted aspartic protease, CtsD, from Aspergillus fumigatus. Protein expression and purification 16 17275325
2016 Txn1, Ctsd and Cdk4 are key proteins of combination therapy with taurine, epigallocatechin gallate and genistein against liver fibrosis in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 27894668
2024 N-glycosylation Modification of CTSD Affects Liver Metastases in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 39716927
2023 Swainsonine inhibits autophagic degradation and causes cytotoxicity by reducing CTSD O-GlcNAcylation. Chemico-biological interactions 14 37442287
2017 Congenital Neuronal Ceroid Lipofuscinosis with a Novel CTSD Gene Mutation: A Rare Cause of Neonatal-Onset Neurodegenerative Disorder. Neuropediatrics 14 29284168
2021 Rapid and Progressive Loss of Multiple Retinal Cell Types in Cathepsin D-Deficient Mice-An Animal Model of CLN10 Disease. Cells 13 33800998
2024 Mechanisms regulating the intracellular trafficking and release of CLN5 and CTSD. Traffic (Copenhagen, Denmark) 9 38272448
2023 TUNEL-positive structures in activated microglia and SQSTM1/p62-positive structures in activated astrocytes in the neurodegenerative brain of a CLN10 mouse model. Glia 6 37571859
2023 Autophagy inhibition mediated by intrauterine miR-1912-3p/CTSD programming participated in the susceptibility to osteoarthritis induced by prenatal dexamethasone exposure in male adult offspring rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 37249374
2008 Sequence identification, tissue distribution and polymorphism of the porcine cathepsin D (CTSD) gene. Animal biotechnology 5 18607787
2025 Plastic additive bisphenol S induces depression by promoting AZU1/CTSD proteins to mediate plasma-related proteins and metabolites: A comprehensive multi-omics analysis. Ecotoxicology and environmental safety 4 40694910
2025 SAMHD1 deficiency disrupts macrophage autophagy-lysosomal homeostasis and promotes inflammation via the mTOR-MITF-CTSD axis in ulcerative colitis. International journal of biological macromolecules 4 40886983
2025 Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload. Acta pharmacologica Sinica 3 39779966
2021 Prenatal-onset of congenital neuronal ceroid lipofuscinosis with a novel CTSD mutation. Birth defects research 3 34491000
2024 CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis. Bone 2 38917962
2024 Studies on the Role of MAP4K2, SPI1, and CTSD in Osteoporosis. Cell biochemistry and biophysics 2 39586961
2021 The c.863A>G (p.Glu288Gly) variant of the CTSD gene is not associated with CLN10 disease. Molecular genetics & genomic medicine 2 34331747
2020 Clinical Prescription-Protein-Small Molecule-Disease Strategy (CPSD), A New Strategy for Chinese Medicine Development: A Case Study in Cardiovascular Diseases. Frontiers in pharmacology 1 32038243
2017 Absence of association of the Ala58Val (rs17571) CTSD gene variant with Parkinson's disease or amyotrophic lateral sclerosis in a Han Chinese population. Neuroscience letters 1 28917980
2026 Snapin mediates neuronal PANoptosis after mild traumatic brain injury via H2S-dependent S-sulfhydration of CTSD. Journal of advanced research 0 41558604
2026 Myeloid KIF13B suppresses the STT3A/CTSD/THBS1 axis to prevent MASH. Hepatology (Baltimore, Md.) 0 41746601
2026 hUMSCs-exo@Cyasterone protects the cell model of steroid-induced femur head necrosis by regulating N-glycosylation modification of CTSD-N258A. PloS one 0 41931502
2026 The miR-214-3p/CTSD Axis Regulates Lysosomal Homeostasis in Porcine Intestinal Epithelial Cells: A Preliminary Study. Biology 0 42117833
2026 Circulatory pro-CTSD binds brain endothelial LRP1 to trigger its lysosomal degradation leading to amyloid beta clearance deficit in Alzheimer's disease mice. Alzheimer's & dementia : the journal of the Alzheimer's Association 0 42162956
2024 CTSD is the key therapeutic target of Jinshui Liujun decoction in treating chronic bronchitis. Natural product research 0 39463007
2024 A Novel Variant of the CTSD Gene Associated with Juvenile-onset Neuronal Ceroid Lipofuscinosis Type 10: A Case Report and Literature Review. Cerebellum (London, England) 0 39656415

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