{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:02:26Z","timestamp":1780452146768,"version":"3.54.1"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"31","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,8,5]]},"abstract":"<jats:p>\n            Lysosomes are central organelles for cellular degradation and energy metabolism. Neuronal ceroid lipofuscinoses (NCLs) are a group of the most common neurodegenerative lysosomal storage disorders characterized by intracellular accumulation of ceroid in neurons. Mutations in\n            <jats:italic>KCTD7<\/jats:italic>\n            , a gene encoding an adaptor of the CUL3-RING E3 ubiquitin ligase (CRL3) complex, are categorized as a unique NCL subtype. However, the underlying mechanisms remain elusive. Here, we report various lysosomal and autophagic defects in KCTD7-deficient cells. Mechanistically, the CRL3-KCTD7 complex degrades CLN5, whereas patient-derived KCTD7 mutations disrupt the interaction between KCTD7-CUL3 or KCTD7-CLN5 and ultimately lead to excessive accumulation of CLN5. The accumulated CLN5 disrupts the interaction between CLN6\/8 and lysosomal enzymes at the endoplasmic reticulum (ER), subsequently impairing ER-to-Golgi trafficking of lysosomal enzymes. Our findings reveal previously unrecognized roles of KCTD7-mediated CLN5 proteolysis in lysosomal homeostasis and demonstrate that KCTD7 and CLN5 are biochemically linked and function in a common neurodegenerative pathway.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abm5578","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T17:59:06Z","timestamp":1659549546000},"source":"Crossref","is-referenced-by-count":22,"title":["KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-3515","authenticated-orcid":true,"given":"Yalan","family":"Wang","sequence":"first","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-4083","authenticated-orcid":true,"given":"Xiaotong","family":"Cao","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Zeng","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Peng","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Shi","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Feng","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0232-3033","authenticated-orcid":true,"given":"Pingzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medical Sciences, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiru","family":"Sun","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-6439","authenticated-orcid":true,"given":"Chenji","family":"Wang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-5264","authenticated-orcid":true,"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering, School of Life Sciences, Children\u2019s Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Fudan University, Shanghai, 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