{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:27:10Z","timestamp":1787016430884,"version":"build-2736575974"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,4,15]]},"abstract":"<jats:p>\n                    Genetic\n                    <jats:italic>CLN5<\/jats:italic>\n                    variants are associated with childhood neurodegeneration and Alzheimer\u2019s disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC\/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (\n                    <jats:italic>S<\/jats:italic>\n                    -depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for\n                    <jats:italic>S<\/jats:italic>\n                    -depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting\n                    <jats:italic>S<\/jats:italic>\n                    -depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of\n                    <jats:italic>S<\/jats:italic>\n                    -depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC\/P60 superfamily of proteins.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abj8633","type":"journal-article","created":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T13:58:36Z","timestamp":1650031116000},"source":"Crossref","is-referenced-by-count":28,"title":["Cln5 represents a new type of cysteine-based\n                    <i>S<\/i>\n                    -depalmitoylase linked to neurodegeneration"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-9468","authenticated-orcid":true,"given":"Anna V.","family":"Luebben","sequence":"first","affiliation":[{"name":"Institute of Inorganic Chemistry, University of G\u00f6ttingen, Tammannstrasse 4, 37077 G\u00f6ttingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-4186","authenticated-orcid":true,"given":"Daniel","family":"Bender","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital Z\u00fcrich, University of Zurich, Steinwiesstrasse 75, 8032 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Fassberg 11, 37077 G\u00f6ttingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital Z\u00fcrich, University of Zurich, Steinwiesstrasse 75, 8032 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-6861","authenticated-orcid":true,"given":"Ilka","family":"Erven","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, Z\u00fclpicher Str.47a, 50674 Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2289-9083","authenticated-orcid":true,"given":"Kay","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institute for Genetics, University of Cologne, Z\u00fclpicher Str.47a, 50674 Cologne, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9642-8244","authenticated-orcid":true,"given":"Johannes","family":"S\u00f6ding","sequence":"additional","affiliation":[{"name":"Quantitative Biology and Bioinformatics and Department of Molecular Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 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Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-1690","authenticated-orcid":true,"given":"Andreas","family":"St\u00e4uble","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital Z\u00fcrich, University of Zurich, Steinwiesstrasse 75, 8032 Z\u00fcrich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7168-0715","authenticated-orcid":true,"given":"Tian","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Chicago, Chicago, IL, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9159-2413","authenticated-orcid":true,"given":"Rahul S.","family":"Kathayat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Chicago, Chicago, IL, 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