ArticleMolecular neurodegeneration2017
The lysosomal protein cathepsin L is a progranulin protease.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial.Nature communications · 2026Trial
- Progranulin deficiency perturbs lipid metabolism in white matter microglia.bioRxiv : the preprint server for biology · 2026Article
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- Article
- Monospecific antibodies reveal reduction of granulins in frontotemporal dementia caused byMolecular neurodegeneration advances · 2026Article
- Intrathalamic delivery of adeno-associated viral vector expressing progranulin as gene therapy for GRN-related frontotemporal dementia.Molecular therapy. Methods & clinical development · 2025Article
- Generation of Induced Pluripotent Stem Cells and Neuroepithelial Stem Cells from a Family with the Pathogenic Variant p.Q337X in Progranulin.International journal of molecular sciences · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.Nature communications · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Retinal biomarkers in schizophrenia spectrum disorders: evidence and implications for the neurodevelopmental and neurodegenerative models.Frontiers in medicine · 2025Review
- Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.Cell reports · 2024Article
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
- An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation.Frontiers in immunology · 2024Article
- Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease.Journal of neuroinflammation · 2023Review
- TMEM106B reduction does not rescue GRN deficiency in iPSC-derived human microglia and mouse models.iScience · 2023Article
- Regulation of extracellular progranulin in medial prefrontal cortex.Neurobiology of disease · 2023Article
- AAV-iScience · 2023Article
- Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors-A Comprehensive Reactivity and Selectivity Study.International journal of molecular sciences · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes frontotemporal lobar degeneration (FTLD), the second most common cause of early-onset dementia. Receptor-mediated lysosomal targeting has been shown to regulate brain PGRN levels, and complete deficiency of PGRN is a direct cause of neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Here we show that the lysosomal cysteine protease cathepsin L (Cat L) can mediate the proteolytic cleavage of intracellular PGRN into poly-granulin and granulin fragments. Further, PGRN and Cat L co-localize in lysosomes of HEK293 cells, iPSC-derived neurons and human cortical neurons from human postmortem tissue. These data identify Cat L as a key intracellular lysosomal PGRN protease, and provides an intriguing new link between lysosomal dysfunction and FTLD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.