Affinage

CTSS

Cathepsin S · UniProt P25774

Round 2 corrected
Length
331 aa
Mass
37.5 kDa
Annotated
2026-04-28
68 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Cathepsin S is a lysosomal cysteine endopeptidase with uniquely broad pH-range activity that serves as the essential protease for MHC class II antigen presentation by cleaving the invariant chain (Ii) to generate αβ-CLIP complexes competent for peptide loading (PMID:8612130, PMID:11884425). Beyond its canonical immune function, CTSS proteolytically processes diverse extracellular and signaling substrates—including JAM-B (enabling blood–brain barrier transmigration and brain metastasis) (PMID:25086747), claudin-1 (disrupting the blood–CSF barrier during aging) (PMID:40015275), PAR2 (acting as a biased agonist coupling to Gαs/cAMP/TRPV4-dependent pain without β-arrestin recruitment) (PMID:25118282), IL-36γ (generating the bioactive psoriasis cytokine) (PMID:28289191), fibronectin (promoting adipogenesis) (PMID:16825321), SLPI (abolishing anti-elastase protection) (PMID:11435427), and BRCA1 (conferring radioresistance in triple-negative breast cancer) (PMID:38613358). CTSS expression is transcriptionally controlled by TFEB downstream of mTORC1 inhibition and post-transcriptionally regulated by ADAR1-mediated A-to-I RNA editing that recruits HuR to stabilize CTSS mRNA (PMID:32640907, PMID:27595325). In macrophages, CTSS promotes autophagic flux and autophagosome–lysosome fusion required for M2 polarization of tumor-associated macrophages, and its secretion is governed by Rab10/mTORC1-dependent lysosomal exocytosis (PMID:24580730, PMID:32640907).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1992 High

    Cloning of CTSS from human alveolar macrophages established it as a cysteine protease with elastinolytic activity retaining substantial function at neutral pH, distinguishing it from other cathepsins and suggesting extracellular roles.

    Evidence cDNA cloning, recombinant expression in COS cells, active-site labeling, elastin degradation at pH 5.5 and 7.0

    PMID:1373132

    Open questions at the time
    • Crystal structure not yet available at this point
    • In vivo substrates unknown
    • Regulatory mechanisms uncharacterized
  2. 1996 High

    Identification of CTSS as the non-redundant protease required for the final step of invariant chain degradation in antigen-presenting cells resolved a long-standing question about how MHC class II molecules acquire antigenic peptides.

    Evidence Specific small-molecule inhibition in B lymphoblastoid cells causing Ii fragment accumulation; in vitro reconstitution showing only purified CTSS (not cathepsins B, H, or D) generates αβ-CLIP from αβIi trimers

    PMID:8612130

    Open questions at the time
    • Cathepsin S contribution to antigen epitope generation versus Ii processing not yet separated
    • Role in non-B cell APCs unresolved
  3. 1998 High

    Subcellular fractionation placed CTSS predominantly in late endosomes and phagosomes of macrophages, while endogenous inhibitors (cystatin C, SCCA1) were characterized kinetically, defining the regulatory framework for CTSS activity in vivo.

    Evidence Organelle fractionation with enzyme activity readouts in J774 macrophages; kinetic inhibition assays with cystatin C mutants and SCCA1–CTSS complex formation

    PMID:7890620 PMID:9545324 PMID:9548757

    Open questions at the time
    • In vivo relevance of SCCA1 inhibition unclear
    • Mechanisms controlling CTSS secretion versus retention unknown
  4. 2006 High

    Demonstration that CTSS degrades extracellular fibronectin to promote preadipocyte differentiation was among the first evidence that CTSS functions outside the endolysosomal compartment in a non-immune, tissue-remodeling context.

    Evidence Primary human preadipocyte cultures treated with recombinant CTSS or specific inhibitor; fibronectin immunostaining and adipocyte marker quantification

    PMID:16825321

    Open questions at the time
    • Fibronectin cleavage site not mapped
    • Contribution of other secreted cathepsins not fully excluded
  5. 2014 High

    A burst of substrate discoveries—JAM-B cleavage enabling blood–brain barrier transmigration for breast cancer metastasis, biased agonist cleavage of PAR2 driving cAMP/TRPV4-dependent pain, and a role in autophagy-mediated M2 macrophage polarization—expanded CTSS biology far beyond invariant chain processing.

    Evidence JAM-B: xenograft metastasis models with combined tumor/macrophage CTSS depletion and pharmacological inhibition [PMID:25086747]; PAR2: cleavage site mapping at E56↓T57 with signaling dissection in HEK cells and PAR2/TRPV4-KO mice [PMID:25118282]; autophagy: CTSS-KO mice with mCherry-GFP-LC3 flux assay and TEM [PMID:24580730]

    PMID:24523067 PMID:24580730 PMID:24875536 PMID:25086747 PMID:25118282

    Open questions at the time
    • JAM-B cleavage site not precisely mapped
    • How CTSS enters the autophagy pathway mechanistically is unclear
    • Whether PAR2 biased agonism by CTSS operates in all tissues unresolved
  6. 2016 High

    Discovery that ADAR1-mediated A-to-I RNA editing in the CTSS 3′ UTR recruits HuR to stabilize CTSS mRNA revealed a novel post-transcriptional regulatory layer responsive to hypoxia and inflammatory cytokines, explaining CTSS upregulation in atherosclerosis.

    Evidence A-to-I editing sequencing, ADAR1 overexpression, HuR RNA immunoprecipitation, mRNA decay assays in endothelial cells, validation in patient atherosclerotic plaques

    PMID:27595325

    Open questions at the time
    • Whether RNA editing regulation extends to non-endothelial cell types in vivo not established
    • Identity of factors competing with HuR for unedited CTSS mRNA unknown
  7. 2017 High

    Identification of CTSS as the major activator of pro-IL-36γ in keratinocytes, generating bioactive IL-36γ-Ser18 that induces psoriasiform changes, directly linked CTSS to psoriasis pathogenesis and a therapeutically actionable substrate.

    Evidence Mass spectrometry cleavage-site identification, siRNA confirmation, functional human skin-equivalent models, elevated CTSS in psoriasis patient samples

    PMID:28289191

    Open questions at the time
    • Whether other cathepsins contribute to IL-36γ activation in vivo not excluded
    • Clinical efficacy of CTSS inhibitors in psoriasis untested
  8. 2020 High

    TFEB was identified as a direct transcriptional activator of CTSS downstream of mTORC1 inhibition, while Rab10/mTORC1 signaling controls CTSS secretion via lysosomal exocytosis, establishing a dual transcriptional–secretory regulatory circuit.

    Evidence ChIP-qPCR, EMSA, and luciferase reporter confirming TFEB binding to CTSS promoter; IP-MS identifying Rab10; in vivo atherosclerosis model with CTSS inhibition

    PMID:32640907

    Open questions at the time
    • Whether TFEB regulation of CTSS operates in professional APCs unknown
    • Rab10-dependent exocytosis mechanism not fully resolved
  9. 2025 High

    CTSS was shown to cleave claudin-1 (CLDN1) at the choroid plexus, establishing it as a mediator of age-related blood–CSF barrier breakdown; inhibiting CTSS or restoring CLDN1 rejuvenated barrier function and brain cognition in aged mice.

    Evidence Choroid plexus macrophage isolation, in vitro CLDN1 cleavage assay, aged mouse models with CTSS inhibition or CLDN1 overexpression, behavioral assessments

    PMID:40015275

    Open questions at the time
    • CLDN1 cleavage site not precisely defined
    • Whether senolytic approaches can substitute for direct CTSS inhibition untested
    • Human translational validation absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full structural basis for CTSS substrate selectivity across its many validated targets, whether CTSS-targeted therapeutics can achieve pathway-selective inhibition without compromising MHC class II-dependent immunity, and how CTSS activity is spatiotemporally coordinated between lysosomal, phagosomal, and extracellular compartments in vivo.
  • No comprehensive structural model explaining selectivity for diverse substrates
  • No clinical trial data for CTSS inhibitors addressing therapeutic window
  • In vivo imaging of CTSS compartment-specific activity lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016787 hydrolase activity 4
Localization
GO:0005576 extracellular region 5 GO:0005764 lysosome 2 GO:0005768 endosome 1
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ADAR1BRCA1CLDN1HURJAM-BPAR2RAB10TFEB

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Human cathepsin S (CTSS) was cloned from alveolar macrophage cDNA and shown to encode a 28-kDa cysteine protease with elastinolytic activity, retaining ~25% of its pH 5.5 elastinolytic activity at pH 7.0, indicating broad pH range activity unlike other cathepsins. cDNA cloning, COS cell expression, active-site labeling with iodinated E-64 analogue, in vitro elastin degradation assay, Northern blot The Journal of biological chemistry High 1373132
1994 The human CTSS gene was mapped to chromosome 1q21 by fluorescence in situ hybridization; the gene structure resembles cathepsin L through exons 1–5 but has larger introns; 5'-flanking region contains AP1 sites and CA microsatellites but no TATA or CAAT box; tissue distribution is restricted (highest in spleen, heart, lung) with immunostaining detecting CTSS only in lung macrophages. Genomic library screening, FISH, Northern blotting, immunostaining The Journal of biological chemistry High 8157683
1995 Cystatin C inhibits cathepsin S with a Ki ~10⁻⁸ M even when the key N-terminal Leu-9 side chain (which contributes 200-fold to cathepsin B affinity and 50-fold to cathepsin L affinity) is absent, demonstrating that the structural determinants for cystatin C selectivity differ between cathepsin S and other cathepsins. Site-directed mutagenesis of cystatin C variants, kinetic inhibition assays against cathepsins B, H, L, S The Journal of biological chemistry High 7890620
1996 Cathepsin S is essential for complete proteolysis of the MHC class II-associated invariant chain (Ii) in B lymphoblastoid cells; specific CTSS inhibition caused accumulation of a 13 kDa Ii fragment, reduced SDS-stable class II complexes, and prevented peptide loading. Purified cathepsin S (but not cathepsins B, H, or D) specifically digested Ii from αβIi trimers in vitro to generate αβ-CLIP complexes capable of binding exogenous peptide. Specific small-molecule inhibition in B cells, in vitro reconstitution with purified cathepsins, Western blot, peptide-binding assay Immunity High 8612130
1998 SCCA1 (serpin squamous cell carcinoma antigen 1) is a potent cross-class inhibitor of cathepsin S, forming stable complexes (t½ > 1155 min) via cleavage between Gly and Ser in its reactive-site loop, analogous to serpin–serine protease interactions; interaction with cathepsin S is 1:1 stoichiometry with second-order rate constants ≥1×10⁵ M⁻¹s⁻¹. Kinetic inhibition assays, SDS-PAGE complex detection, reactive-site loop cleavage mapping Biochemistry High 9548757
1998 In J774 macrophages, the bulk of cellular cathepsin S is concentrated in late endosomes (as opposed to cathepsin H enriched in early endosomes), and cathepsin S is present in phagosomal fractions, establishing its trafficking itinerary within the endolysosomal system. Subcellular fractionation, enrichment of early endosomes/late endosomes/lysosomes/phagosomes, enzyme activity assays The Journal of biological chemistry High 9545324
2001 Cathepsin S (along with B and L) cleaves and inactivates secretory leucoprotease inhibitor (SLPI) between Thr67 and Tyr68, eliminating SLPI's active site and its anti-neutrophil elastase capacity; cathepsins L and S inactivated a 400-fold excess of SLPI within 15 min in catalytic fashion. In vitro cleavage assay with purified cathepsins, sequencing of cleavage site, anti-elastase activity assay, analysis of emphysema epithelial lining fluid The Journal of biological chemistry High 11435427
2002 Cathepsin S expressed in embryonic fibroblasts mediates invariant chain degradation and alters the peptide repertoire presented by MHC class II molecules; for a subset of antigens, cathepsin S is required for epitope generation, as shown by T cell hybridoma assays and mass spectrometric analysis of eluted peptides. Reconstituted fibroblast cell lines expressing cathepsin L or S, T cell hybridoma assays, mass spectrometry of MHC II-eluted peptides Journal of immunology High 11884425
2006 Cathepsin S promotes human preadipocyte differentiation at least in part by degrading fibronectin in the extracellular matrix; CTSS activity was highest in preadipocyte culture medium and decreased during differentiation; exogenous recombinant CTSS increased adipogenesis and markedly reduced the fibronectin network, while specific CTSS inhibition reduced lipid content and adipocyte marker expression 2-fold. Primary human preadipocyte cultures, recombinant CTSS treatment, specific inhibitor treatment, fibronectin immunostaining, adipocyte marker expression Endocrinology High 16825321
2011 Proteomic identification of cathepsin S cleavage sites (PICS) at pH 6.0 and 7.5 revealed that its specificity is primarily guided by aliphatic residues in P2, with limited importance of prime-site residues; the specificity profiles at both pH values were highly similar, consistent with broad pH activity. PICS (proteomic identification of protease cleavage sites) with mass spectrometry at pH 6.0 and 7.5 Journal of proteome research High 21967108
2014 Cathepsin S specifically mediates breast-to-brain metastasis by proteolytic processing of the junctional adhesion molecule JAM-B, enabling blood-brain barrier transmigration; both macrophage- and tumor cell-derived CTSS contribute, and only combined depletion significantly reduced brain metastasis in vivo; pharmacological inhibition of CTSS significantly reduced experimental brain metastasis. Xenograft metastasis models (xenograft), CTSS depletion from tumor cells and macrophages separately and combined, in vitro BBB transmigration assay, proteolytic substrate identification (JAM-B cleavage), pharmacological inhibition in vivo Nature cell biology High 25086747
2014 CD47-positive hepatocellular carcinoma (HCC) tumor-initiating cells preferentially secrete cathepsin S, which regulates liver tumor-initiating cell properties through a CTSS/protease-activated receptor 2 (PAR2) signaling loop; knockdown of CD47 suppressed this CTSS/PAR2 axis and reduced HCC growth in vivo. CD47 knockdown (morpholino), CTSS secretion measurement, PAR2 signaling assays, in vivo HCC tumor models Hepatology High 24523067
2014 Cathepsin S cleaves PAR2 at E56↓T57 (distinct from the canonical trypsin site R36↓S37), acting as a biased agonist: it stimulates PAR2 coupling to Gαs/cAMP but does not mobilize intracellular Ca²⁺, activate ERK1/2, recruit β-arrestins, or induce PAR2 endocytosis. Cat-S causes PAR2- and TRPV4-dependent inflammation and hyperalgesia via adenylyl cyclase/PKA mechanisms in mouse dorsal root ganglia and in vivo. In vitro cleavage site mapping, HEK/KNRK cell signaling assays (cAMP, Ca²⁺, ERK, β-arrestin), Xenopus oocyte electrophysiology, mouse DRG nociceptor recordings, PAR2/TRPV4 knockout mice, intraplantar injection model The Journal of biological chemistry High 25118282
2014 Cathepsin S is required for autophagic flux (including autophagosome-lysosome fusion) in tumor-associated macrophages (TAMs); CTSS knockout inhibited M2 macrophage polarization during tumor development and reduced tumor growth and metastasis; Cat S promotes M2 polarization through activation of autophagy. Cat S knockout mice, subcutaneous and hepatic metastasis tumor models, mCherry-GFP-LC3 autophagy flux assay, DQ-BSA degradation, TEM, flow cytometry for macrophage phenotype Molecular cancer High 24580730
2014 Inhibition of cathepsin S in glioblastoma cells induces autophagy and mitochondrial apoptosis via ROS-mediated suppression of the PI3K/AKT/mTOR/p70S6K pathway and activation of JNK signaling; blocking autophagy attenuated cathepsin S inhibition-induced apoptosis, placing autophagy upstream of apoptosis in this pathway. Small-molecule CTSS inhibition, siRNA knockdown, ROS measurement, Western blot for PI3K/AKT/mTOR/JNK pathway components, autophagy inhibitors, cell death assays Toxicology letters Medium 24875536
2016 CTSS mRNA is highly edited at its 3' UTR by ADAR1 via adenosine-to-inosine (A-to-I) RNA editing within AluJo/AluSx+ inverted repeat elements that form a long stem-loop; editing enables recruitment of the stabilizing RNA-binding protein HuR to the CTSS 3' UTR, controlling CTSS mRNA stability and expression. Hypoxia and inflammatory cytokines (IFN-γ, TNF-α) induce CTSS RNA editing and increase cathepsin S expression in endothelial cells. A-to-I editing sequencing, ADAR1 overexpression, RIP (RNA immunoprecipitation) of HuR, mRNA stability assays, patient atherosclerosis samples, cytokine treatment Nature medicine High 27595325
2017 Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ in keratinocytes; CTSS cleaves pro-IL-36γ to generate the bioactive form IL-36γ-Ser18; this product induces psoriasiform changes in human skin-equivalent models; CTSS activity is strongly upregulated in psoriasis patient samples. Keratinocyte activity assay, small-molecule inhibitors, siRNA gene silencing, mass spectrometry cleavage-site identification, human skin-equivalent models, patient psoriasis samples Proceedings of the National Academy of Sciences of the United States of America High 28289191
2020 Nicotine activates autophagy in vascular smooth muscle cells by inhibiting mTORC1 activity, promoting nuclear translocation of TFEB, which directly binds the CTSS promoter (demonstrated by ChIP-qPCR, EMSA, and luciferase reporter assay) to upregulate CTSS expression. mTORC1 inhibition promotes lysosomal exocytosis and CTSS secretion via a mechanism involving Rab10; CTSS upregulation promotes vascular smooth muscle cell migration and atherosclerosis in vivo. Western blot, immunofluorescent staining, ChIP-qPCR, EMSA, luciferase reporter assay, IP-MS (Rab10 interaction), live cell imaging, in vivo atherosclerosis model with CTSS inhibition Arteriosclerosis, thrombosis, and vascular biology High 32640907
2022 CTSS directly disrupts epithelial barrier integrity in corneal epithelial cells; TNF-α and hyperosmolarity induce CTSS expression, while IL-37 suppresses TNF-α and CTSS expression and restores tight junction (ZO-1, occludin, claudin-1) and adherens junction (E-cadherin) protein integrity under hyperosmotic stress. Primary human corneal epithelial cell culture, hyperosmolar stress model, RT-qPCR, ELISA, immunofluorescent confocal microscopy, rhIL-37 and rhTNF-α treatment The ocular surface Medium 36208723
2023 CTSS deletion in mice reduced stress-related carotid artery thrombus formation following FeCl3 induction; mechanistically, CTSS knockout decreased PAI-1, vWF, inflammatory mediators (TNF-α, IL-1β, TLR-4), apoptosis markers (cleaved caspase-3, cytochrome c), oxidative stress markers (gp91phox, p22phox), and MMPs, while increasing ADAMTS13, SOD-1/2, eNOS, p-Akt, Bcl-2, and p-Erk1/2. In vitro, CTSS silencing/overexpression respectively reduced/increased apoptosis of HUVECs exposed to stress serum. CTSS-/- mice vs. wild-type, FeCl3 carotid thrombosis model, immobilization stress, Western blot, qPCR, pharmacological CTSS inhibition, CTSS siRNA and overexpression in HUVECs Arteriosclerosis, thrombosis, and vascular biology Medium 37128920
2023 vNAR (Variable New Antigen Receptor) antibody fragments identified by phage display against human proCTSS inhibit CTSS activity by preventing the activation of proCTSS to its mature form (a novel inhibitory mechanism), and can inhibit CTSS activity intracellularly when expressed as intrabodies, reducing tumor cell invasion in vitro. Phage display panning, ELISA, SPR binding assays, recombinant enzyme activity assays, intrabody expression, tumor cell invasion assay Frontiers in pharmacology Medium 38116078
2024 Cathepsin S mediates BRCA1 protein degradation in triple-negative breast cancer cells; RT-induced CTSS increase causes radioresistance by suppressing BRCA1-mediated apoptosis. A novel CTSS inhibitor (TS-24) increased BRCA1 protein levels and radiosensitized TNBC cells in vitro and in a xenograft model via BRCA1-mediated apoptosis. CTSS enzyme assay, in silico docking, Western blot (BRCA1 protein levels), promoter assay, clonogenic survival assay, cell death assay, TNBC xenograft mouse model, immunohistochemistry Cancer science Medium 38613358
2024 In IBS, enhanced interaction between PDIA3 and STAT3 at the dendritic cell membrane reduces nuclear translocation of phosphorylated STAT3 (p-STAT3), which in turn increases CTSS and MHC-II levels; activated DCs promote CD4+ T cell proliferation and cytokine secretion (IL-4, IL-6, IL-9, TNF-α), contributing to IBS pathology. Co-IP (PDIA3-STAT3 interaction), Western blot, siRNA PDIA3 knockdown, IBS rat model, punicalagin treatment Heliyon Medium 39286134
2025 Macrophage-derived cathepsin S (CTSS), secreted from choroid plexus (CP) macrophages, is upregulated in aged CP due to increased cell senescence and cleaves the tight junction component claudin 1 (CLDN1), thereby impairing the blood-CSF barrier. Inhibiting CTSS or upregulating CLDN1 in aged CP rejuvenates the blood-CSF barrier and brain functions in aged animals. CP macrophage isolation, CTSS secretion measurement, in vitro CLDN1 cleavage assay, aged mouse models with CTSS inhibition or CLDN1 overexpression, brain function assessments Neuron High 40015275
2025 CTSS contributes to airway neutrophilic inflammation in mixed granulocytic asthma through an Akt-dependent pathway; intratracheal instillation of recombinant CTSS induced neutrophil recruitment and overproduction of soluble E-cadherin (sE-cadherin) in lung tissue, which was attenuated by Akt signaling inhibition; pharmacological CTSS antagonism (LY3000328) decreased airway hyperresponsiveness and neutrophil accumulation and IL-17/sE-cadherin release in murine MGA models. Recombinant CTSS intratracheal instillation, LY3000328 (CTSS antagonist), Akt inhibition, two murine MGA models (TDI and OVA/CFA), bronchoalveolar lavage cell counts, cytokine measurement Respiratory research Medium 39719614
2026 Macrophage-derived amphiregulin (AREG) activates EGFR on Schwann cells and upregulates cathepsin S (CTSS) expression, enhancing Schwann cell phagocytic capability for myelin debris clearance after nerve injury; Areg conditional knockout impaired Schwann cell phagocytosis, which was rescued by CTSS restoration. Areg conditional knockout (cKO) mouse model, conditioned medium experiments, CTSS rescue in Schwann cells, phagocytosis assays, Wallerian degeneration model Molecular neurobiology Medium 41708964

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity 448 8612130
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2014 Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nature cell biology 318 25086747
1992 Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. The Journal of biological chemistry 260 1373132
1998 Cross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: a kinetic analysis. Biochemistry 242 9548757
2016 Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nature medicine 241 27595325
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2014 Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology (Baltimore, Md.) 185 24523067
1994 Human cathepsin S: chromosomal localization, gene structure, and tissue distribution. The Journal of biological chemistry 166 8157683
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1998 Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes. The Journal of biological chemistry 160 9545324
2014 Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4. The Journal of biological chemistry 159 25118282
2011 Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. Journal of proteome research 157 21967108
2001 Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. The Journal of biological chemistry 152 11435427
2006 The DNA sequence and biological annotation of human chromosome 1. Nature 144 16710414
2002 A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation. Journal of immunology (Baltimore, Md. : 1950) 137 11884425
2014 Inhibition of cathepsin S induces autophagy and apoptosis in human glioblastoma cell lines through ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling pathways. Toxicology letters 132 24875536
2017 Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ. Proceedings of the National Academy of Sciences of the United States of America 125 28289191
2006 Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology 115 16825321
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2014 Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization. Molecular cancer 112 24580730
1995 Structural basis for the biological specificity of cystatin C. Identification of leucine 9 in the N-terminal binding region as a selectivity-conferring residue in the inhibition of mammalian cysteine peptidases. The Journal of biological chemistry 108 7890620
2014 Tear cathepsin S as a candidate biomarker for Sjögren's syndrome. Arthritis & rheumatology (Hoboken, N.J.) 106 24644101
2022 Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential. Molecular aspects of medicine 105 35868042
1995 The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study. The American journal of pathology 100 7717452
2001 Expression of cathepsins B and S in the progression of prostate carcinoma. International journal of cancer 99 11241311
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
2022 BCG hydrogel promotes CTSS-mediated antigen processing and presentation, thereby suppressing metastasis and prolonging survival in melanoma. Journal for immunotherapy of cancer 37 35732347
2019 Fisetin Suppresses the Proliferation and Metastasis of Renal Cell Carcinoma through Upregulation of MEK/ERK-Targeting CTSS and ADAM9. Cells 33 31438640
2021 Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice. Aging 29 34077394
2023 CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl3 Model. Arteriosclerosis, thrombosis, and vascular biology 27 37128920
2020 Nicotine Modulates CTSS (Cathepsin S) Synthesis and Secretion Through Regulating the Autophagy-Lysosomal Machinery in Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 24 32640907
2022 Imbalanced IL-37/TNF-α/CTSS signaling disrupts corneal epithelial barrier in a dry eye model in vitro. The ocular surface 22 36208723
2021 Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells. International journal of molecular sciences 22 34208434
2018 Association between CTSS gene polymorphism and the risk of acute atherosclerotic cerebral infarction in Chinese population: a case-control study. Bioscience reports 13 30341237
2025 Macrophage-derived CTSS drives the age-dependent disruption of the blood-CSF barrier. Neuron 12 40015275
2012 Dietary factors impact on the association between CTSS variants and obesity related traits. PloS one 12 22844403
2024 Radiosensitizing effect of a novel CTSS inhibitor by enhancing BRCA1 protein stability in triple-negative breast cancer cells. Cancer science 10 38613358
2021 Modulation of Cathepsin S (CTSS) Regulates the Secretion of Progesterone and Estradiol, Proliferation, and Apoptosis of Ovarian Granulosa Cells in Rabbits. Animals : an open access journal from MDPI 10 34199180
2020 MiR-491-3p is down-regulated in postmenopausal osteoporosis and affects growth, differentiation and apoptosis of hFOB1.19 cells through targeting CTSS. Folia histochemica et cytobiologica 10 32176315
2010 Association between cathepsin L (CTSL) and cathepsin S (CTSS) polymorphisms and meat production and carcass traits in Italian Large White pigs. Meat science 10 20374908
2020 Genome-wide identification, expression signature and immune functional analysis of two cathepsin S (CTSS) genes in turbot (Scophthalmus maximus L.). Fish & shellfish immunology 8 32315741
2003 CTSS: a robust and efficient method for protein structure alignment based on local geometrical and biological features. Proceedings. IEEE Computer Society Bioinformatics Conference 8 16452791
2000 Human cathepsin S gene (CTSS) promoter -25G/A polymorphism. Journal of human genetics 8 10721671
2025 Bioinformatics-based identification of CTSS, DOK2, and ENTPD1 as potential blood biomarkers of schizophrenia. BMC psychiatry 5 39972407
2024 Cathepsin S (CTSS) in IgA nephropathy: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target. Frontiers in immunology 5 38979419
2018 Hypothesis: Is there a link between the immune response to Human Herpes Virus type 6Α (HHV-6Α) infection and the interaction network (interactome) of the genes encoding the CTSS, PTX3, CHI3L1, Mx1, CXCL16, BIRC3 and BST2 proteins? Medical hypotheses 5 29447938
2023 Noise exposure increase apoptosis in the hippocampus of AD mice through the upregulation of CTSS. Biochemical and biophysical research communications 4 37801777
2023 Effect of CTSS non-synonymous mutations on litter size in Qianbei Ma goats. Frontiers in veterinary science 4 38089704
2024 CTSS contributes to airway neutrophilic inflammation in mixed granulocytic asthma. Respiratory research 3 39719614
2025 Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS. Scientific reports 2 39824912
2025 Identifying a gene signature for age-related hearing loss through machine learning and revealing the effect of the CTSS on the mice cochlea. Biogerontology 2 40461927
2025 Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis. Investigative ophthalmology & visual science 2 40557874
2024 The PDIA3-STAT3 protein complex regulates IBS formation and development via CTSS/MHC-II pathway-mediated intestinal inflammation. Heliyon 2 39286134
2023 Evaluation of variable new antigen receptors (vNARs) as a novel cathepsin S (CTSS) targeting strategy. Frontiers in pharmacology 2 38116078
2009 CTSS promoter -25G/A: not a risk factor for CHD in Chinese. Acta cardiologica 2 19593952
2025 CTSS and CD53: Emerging m6A methylation markers in diabetic kidney disease pathogenesis and their clinical implications. BMC nephrology 1 40624623
2025 LINC02099 Promotes Retinal Extracellular Matrix Deposition in Diabetic Mice Via the miRNA-214-3p/CTSS Axis. Investigative ophthalmology & visual science 1 40965405
2024 Potential role of CTSS in AMDImmune modulatory and anti-angiogenic effects of cathepsin S knockdown in ARPE-19 cells. Experimental eye research 1 38914301
2026 Macrophage-Derived Amphiregulin Enhances Schwann Cell Phagocytosis Through the EGFR/CTSS Signaling Pathway. Molecular neurobiology 0 41708964
2026 Single-Cell Transcriptomics Reveals Riluzole as an Osteoarthritis Candidate Drug via OB-NE Signaling Modulation and CTSS/NOS1 Inhibition. Drug design, development and therapy 0 41993107
2025 Genetic and functional validation of CTSS in regulating intramuscular fat content of Duroc-Landrace-Yorkshire pigs. Animal genetics 0 40251967
2025 CTSS in the tumor microenvironment links immune escape and immunotherapy sensitivity in kidney renal clear cell carcinoma. Discover oncology 0 40730712