{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:04:53Z","timestamp":1776877493724,"version":"3.51.2"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Batten disease is a devastating, childhood, rare neurodegenerative disease characterised by the rapid deterioration of cognition and movement, leading to death within ten to thirty years of age. One of the thirteen Batten disease forms, CLN5 Batten disease, is caused by mutations in the CLN5 gene, leading to motor deficits, mental deterioration, cognitive impairment, visual impairment, and epileptic seizures in children. A characteristic pathology in CLN5 Batten disease is the defects in lysosomes, leading to neuronal dysfunction. In this study, we aimed to investigate the lysosomal changes in CLN5-deficient human neurons. We used an induced pluripotent stem cell system, which generates pure human cortical-like glutamatergic neurons. Using CRISPRi, we inhibited the expression of CLN5 in human neurons. The CLN5-deficient human neurons showed reduced acidic organelles and reduced lysosomal enzyme activity measured by microscopy and flow cytometry. Furthermore, the CLN5-deficient human neurons also showed impaired lysosomal movement\u2014a phenotype that has never been reported in CLN5 Batten disease. Lysosomal trafficking is key to maintain local degradation of cellular wastes, especially in long neuronal projections, and our results from the human neuronal model present a key finding to understand the underlying lysosomal pathology in neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/biom11101412","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T10:39:20Z","timestamp":1632739160000},"page":"1412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Deficiency of the Lysosomal Protein CLN5 Alters Lysosomal Function and Movement"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-2845","authenticated-orcid":false,"given":"Indranil","family":"Basak","sequence":"first","affiliation":[{"name":"Brain Health Research Centre and Genetics Otago, Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Brain Health Research Centre and Genetics Otago, Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Ward","sequence":"additional","affiliation":[{"name":"National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Brain Health Research Centre and Genetics Otago, Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9011, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4735","DOI":"10.1007\/s00018-021-03813-x","article-title":"A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis","volume":"78","author":"Basak","year":"2021","journal-title":"Cell. 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