| 2016 |
Under homeostatic conditions, CTSB cleaves the calcium channel MCOLN1/TRPML1 in lysosomes, thereby maintaining suppression of the transcription factor TFEB and reducing expression of lysosomal and autophagy-related proteins, controlling the number of lysosomes and autophagosomes in the cell. |
Genetic knockout/inhibition with functional readout (lysosome/autophagosome counts, TFEB activity, MCOLN1 cleavage assay) |
Autophagy |
Medium |
27786577
|
| 2021 |
Cancer cell-derived CST6 (cystatin 6) enters osteoclasts by endocytosis and suppresses CTSB proteolytic activity; CTSB normally degrades SPHK1, so CTSB inhibition leads to SPHK1 upregulation, which suppresses osteoclast maturation by inhibiting RANKL-induced p38 activation. |
In vitro osteoclastogenesis assay, CTSB activity assay, western blot for SPHK1 and p38 phosphorylation, in vivo metastasis model |
Theranostics |
Medium |
34815788
|
| 2022 |
In macrophages, HDAC3 deficiency leads to elevated CTSB expression (via histone acetylation), and the resulting excess CTSB degrades RIP1 (RIPK1) protein, reducing TNFα-mediated NF-κB activation and inflammatory response. |
HDAC3 knockout macrophages, western blot for RIP1 degradation, immunofluorescence, RNAseq, CTSB inhibitor rescue experiments |
Cell & Bioscience |
Medium |
35658939
|
| 2014 |
CTSB promotes preadipocyte differentiation by degrading fibronectin (Fn), a key extracellular matrix component and target gene of the Wnt/β-catenin pathway; CTSB degrades Fn and attenuates Wnt/β-catenin signaling to promote adipogenesis. |
CTSB overexpression/inhibition in primary porcine preadipocytes, lipid accumulation assay, western blot for β-catenin, LiCl (Wnt activator) rescue experiment |
Molecular and cellular biochemistry |
Low |
24878992
|
| 2023 |
In sepsis-induced acute kidney injury, LPS induces lysosomal membrane permeabilization (LMP), causing CTSB release into the cytoplasm, which then activates the mitochondrial apoptosis pathway; CTSB inhibitor CA-074 reverses LPS-induced apoptosis, mitochondrial membrane potential loss, and activation of mitochondrial apoptosis markers. |
LPS-treated HK-2 cells, CTSB activity assay, acridine orange staining (LMP), JC-1 (mitochondrial membrane potential), Annexin V/PI, CA-074 inhibitor rescue, western blot |
Frontiers in immunology |
Medium |
36713420
|
| 2025 |
CTSB degrades ferroportin (FPN) in macrophages, disrupting iron homeostasis and promoting ferroptosis; CTSB was shown to directly bind FPN and negatively regulate its protein level. |
Co-IP/binding assay for CTSB-FPN interaction, CTSB knockdown/inhibition, western blot for FPN, ferroptosis markers, ApoE KO and HFD rat AS models, single-cell transcriptomics |
Molecular and cellular biochemistry |
Medium |
39960586
|
| 2025 |
MINPP1 stabilizes CTSB expression by modulating its K33-linked deubiquitination via ZRANB1 (a deubiquitinase), thereby promoting ferroptosis in HBV-positive hepatocellular carcinoma cells. |
Immunoprecipitation for ubiquitin modifications, immunofluorescence, CTSB K33-ubiquitination site mapping, in vivo tumor assays |
Biology direct |
Medium |
41035046
|
| 2025 |
ETS1 transcription factor promotes the transcription of CTSB (and MMP13) during the differentiation of septoclasts from pericytes; ETS1 siRNA significantly reduced CTSB expression in primary septoclast cultures. |
RNA-seq of isolated septoclasts vs pericytes, ETS1 siRNA knockdown in primary cultures, RT-qPCR |
Cell and tissue research |
Low |
40387924
|
| 2025 |
METTL3 upregulates CTSB expression in chondrocytes through m6A methylation of CTSB mRNA; the protective effects of METTL3 silencing against IL-1β-induced chondrocyte injury depend on downstream CTSB downregulation. |
m6A RNA immunoprecipitation assay, dual-luciferase reporter assay, METTL3/CTSB siRNA knockdown, western blot, flow cytometry |
Journal of orthopaedic surgery and research |
Medium |
41466292
|
| 2025 |
OGT-mediated O-GlcNAcylation of CTSB promotes its lysosomal retention and reduces its maturation; reduced O-GlcNAcylation (through OGT downregulation) lowers ROS, attenuates lysosomal membrane permeabilization, limits cytoplasmic CTSB leakage, and suppresses NLRP3 inflammasome activation in astrocytes. |
Co-IP for OGT-CTSB interaction, O-GlcNAcylation analysis, immunofluorescence for CTSB/LAMP1 colocalization, DHE staining for ROS, western blot |
Journal of ethnopharmacology |
Medium |
41391522
|
| 2020 |
A gain-of-function missense mutation in CTSB results in increased cathepsin B endopeptidase proteolytic activity, as confirmed by a cathepsin B enzymatic assay, and causes palmoplantar keratoderma in a dominant fashion. |
Whole exome sequencing, cathepsin B enzymatic activity assay, protein structural modelling |
Clinical and experimental dermatology |
Medium |
32683719
|
| 2017 |
Duplicated enhancer region upstream of CTSB drives increased CTSB expression specifically in epidermal keratinocytes; the enhancer activity correlates with CTSB expression in differentiating keratinocytes, establishing CTSB overexpression as the cause of keratolytic winter erythema (KWE). |
Targeted resequencing, SNP array, whole-genome sequencing, enhancer activity reporter assay, qPCR, immunohistochemistry; segregation analysis in South African and Norwegian families |
American journal of human genetics |
High |
28457472
|
| 2023 |
Nuclear translocation of CTSB in retinoblastoma cells promotes DNA damage and cell cycle arrest by inhibiting BRCA1 expression, and activates the STAT3/STING1 pathway to induce lysosomal stress, ferroptosis, and autophagy. |
CTSB overexpression with nuclear translocation, comet assay (DNA damage), flow cytometry (cell cycle/apoptosis/ferroptosis), western blot for BRCA1 and STAT3/STING1 pathway, CCK-8, RT-qPCR |
Molecular biotechnology |
Low |
38159170
|
| 2024 |
Lysosomal CTSB activity is required for efficient phagolysosomal fusion and acidification in microglia; myeloid-specific CTSB knockdown in zebrafish led to dysmorphic microglia containing undigested dead cells and accumulation of apoptotic cells during brain development, phenocopied in Ctsb-deficient mice. |
Myeloid-specific CTSB knockdown in zebrafish, Ctsb global KO mice, live imaging of phagolysosomal fusion and acidification, apoptosis markers, behavioral assays |
bioRxivpreprint |
Medium |
|
| 2025 |
Nervous system-specific double knockout of CtsB and CtsL in mice leads to selective loss of specific Purkinje cell subpopulations (phospholipase C β4-positive, Zebrin II-negative), ubiquitin-positive aggregate accumulation in Purkinje cell perikarya and axons reflecting impaired autophagy-lysosomal degradation, and neuronal loss in thalamic nuclei. |
Conditional double-knockout mice (Nestin-Cre; CTSBflox/flox; CTSLflox/flox), electron microscopy, immunohistochemistry, behavioral testing |
The American journal of pathology |
Medium |
40320169
|
| 2024 |
Beauvericin (BEA) directly interacts with CTSB and acts as an uncompetitive inhibitor of its enzymatic activity; NMR analyses confirmed direct BEA-CTSB interaction, and enzyme kinetics established uncompetitive inhibition mechanism. |
NMR spectroscopy (direct interaction), enzyme kinetics (uncompetitive inhibition), molecular docking (binding site), CTSB activity assay in BMDCs and THP-1-derived DCs |
bioRxivpreprint |
Medium |
|
| 2025 |
Elevated lysosomal CTSB and cytoplasmic CTSB leakage in mouse models of neurological lysosomal storage diseases (MPS IIIC and sialidosis) triggers amyloidogenesis in cortical neurons; CTSB-deficient MPS IIIC mice or animals treated with irreversible CTSB inhibitor E64 showed drastic reduction of Thioflavin-S/APP-positive amyloid deposits and restoration of autophagy. |
Ctsb knockout in MPS IIIC mouse model, chronic E64 (CTSB inhibitor) treatment, Thioflavin-S/APP staining, P62/LC3 puncta, behavioral assays, cytoplasmic CTSB localization |
bioRxivpreprint |
Medium |
|
| 2025 |
Extralysosomal CTSB cleaves the C-terminal region of TAF1 (a core TFIID component) in oligodendrocytes during multiple sclerosis progression, impairing RNAPII promoter-proximal pausing and reducing expression of oligodendroglial myelination genes. |
Mass spectrometry/proteomics of MS brains, endoproteolysis assay for TAF1 cleavage by CTSB, Taf1 C-terminal deletion mouse model, brain transcriptomics, CTSB inhibitor experiments |
bioRxivpreprint |
Medium |
|
| 2025 |
AAV-mediated overexpression of CTSB in skeletal muscle of APP/PS1 Alzheimer's disease mice improves motor coordination, memory function, and adult hippocampal neurogenesis, and shifts hippocampal, muscle, and plasma proteomic profiles toward wild-type; wildtype mice receiving Ctsb muscle overexpression developed memory deficits. |
AAV-vector muscle overexpression in APP/PS1 mice, behavioral testing (memory, motor), hippocampal neurogenesis assay, multi-tissue proteomics |
bioRxivpreprint |
Low |
|
| 2025 |
CTSB cleaves sialin (a lysosomal nitrate transporter) to generate a proteolytic fragment called Sialin2 that localizes to mitochondria and scaffolds LKB1-AMPK complexes to activate AMPK-dependent mitochondrial biogenesis. |
Cryo-EM structure of Sialin2, microscale thermophoresis (nitrate binding), CTSB cleavage assay, subcellular fractionation, Co-IP for LKB1-AMPK scaffold |
bioRxivpreprint |
Low |
|
| 2025 |
CTSB promotes NLRP3-mediated pyroptosis in vascular endothelial cells (HUVECs) through NF-κB activation after being released from lysosomes upon lysosomal damage caused by Na+/Ca2+ overload; lentiviral CTSB overexpression increased and CTSB silencing decreased NLRP3-mediated pyroptosis. |
Lentiviral CTSB overexpression and silencing in HUVECs, western blot for NF-κB/NLRP3/GSDMD pathway, LDH/IL-1β release assay, ion overload measurement |
Biochemical pharmacology |
Medium |
40058708
|