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Intriguingly, CLN7 genetic variants have also been associated with retinopathies, amyotrophic lateral sclerosis, and frontotemporal dementia.\n                    <jats:italic>CLN7<\/jats:italic>\n                    encodes a transmembrane protein localizing to endolysosomal membranes with outward-facing chloride channel activity. Loss of CLN7 function results in cortical neurons accumulating swollen lipofuscin-containing lysosomes, leading to neuroinflammation and neurodegeneration. The molecular mechanisms underlying CLN7 BD neuropathology are not completely understood. We have generated iPSC lines from two CLN7 BD patients and age-matched unaffected controls to interrogate intracellular molecular phenotypes in iPSC-derived neural progenitor cells (iNPC). Taking a multi-omics approach we have identified disease-modified activities in endolysosomal transport in iNPC\n                    <jats:sup>BD<\/jats:sup>\n                    that lead to lysosomal dysfunction and decreased mitophagy, resulting in the accumulation of metabolically defective mitochondria. We further observe a breakdown in nuclear functions that centre on RNA processing and nuclear export, linking to CLN7 protein interactions at the stress granule. We have identified dual and distinct functions for CLN7, promoting cell survival during the cellular stress response. CLN7 loss of function in BD results in neuronal apoptosis.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-08063-4","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T11:23:06Z","timestamp":1761909786000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CLN7 protein functions at the interface between endolysosomes and stress granules to promote cell survival"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1242-1315","authenticated-orcid":false,"given":"Aseel","family":"Sharaireh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5334-3344","authenticated-orcid":false,"given":"Marta","family":"Guevara-Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Ludlaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Humphries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Dowsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Counsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Unwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Mole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahad A.","family":"Rahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-9115","authenticated-orcid":false,"given":"Tristan R.","family":"McKay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"8063_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S1474-4422(18)30368-5","volume":"18","author":"SE Mole","year":"2019","unstructured":"Mole SE, Anderson G, Band HA, Berkovic SF, Cooper JD, Kleine Holthaus SM, et al. 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Patient fibroblasts were received from the UCL NCL repository, distributed under a Material Transfer Agreement between UCL and Manchester Metropolitan University. Informed consent to generate cell lines used in this research was obtained from all human subjects through the UCL Research Ethics Committee, and experiments conformed to the WMA Declaration of Helsinki and to the principles set out in the USA Department of Health and Human Services Belmont Report. Local ethical approval was gained through the Manchester Metropolitan University Research Ethics and Governance Committee (EthOS Ref: 53114).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approvals and consent to participate"}}],"article-number":"772"}}