{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:55:12Z","timestamp":1781081712535,"version":"3.54.1"},"reference-count":48,"publisher":"Portland Press Ltd.","issue":"12","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,25]]},"abstract":"<jats:p>CLN5 is a soluble endolysosomal protein whose function is poorly understood. Mutations in this protein cause a rare neurodegenerative disease, neuronal ceroid lipofuscinosis (NCL). We previously found that depletion of CLN5 leads to dysfunctional retromer, resulting in the degradation of the lysosomal sorting receptor, sortilin. However, how a soluble lysosomal protein can modulate the function of a cytosolic protein, retromer, is not known. In this work, we show that deletion of CLN5 not only results in retromer dysfunction, but also in impaired endolysosome fusion events. This results in delayed degradation of endocytic proteins and in defective autophagy. CLN5 modulates these various pathways by regulating downstream interactions between CLN3, an endolysosomal integral membrane protein whose mutations also result in NCL, RAB7A, and a subset of RAB7A effectors. Our data support a model where CLN3 and CLN5 function as an endolysosomal complex regulating various functions.<\/jats:p>","DOI":"10.1042\/bcj20210171","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T08:40:16Z","timestamp":1622536816000},"page":"2339-2357","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["CLN5 and CLN3 function as a complex to regulate endolysosome function"],"prefix":"10.1042","volume":"478","author":[{"given":"Seda","family":"Yasa","sequence":"first","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, Institut national de la recherche scientifique, Laval H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Sauvageau","sequence":"additional","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, Institut national de la recherche scientifique, Laval H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Modica","sequence":"additional","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, Institut national de la recherche scientifique, Laval H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-9594","authenticated-orcid":false,"given":"Stephane","family":"Lefrancois","sequence":"additional","affiliation":[{"name":"Centre Armand-Frappier Sant\u00e9 Biotechnologie, Institut national de la recherche scientifique, Laval H7V 1B7, Canada"},{"name":"Department of Anatomy and Cell Biology, McGill University, Montreal H3A 0C7, Canada"},{"name":"Centre d'Excellence en Recherche sur les Maladies Orphelines - Fondation Courtois (CERMO-FC), Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montr\u00e9al H2X 3Y7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"2021112218223135600_BCJ-2021-0171C1","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","article-title":"Genetics of the neuronal ceroid lipofuscinoses (Batten disease)","volume":"1852","year":"2015","journal-title":"Biochim. 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