{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:04:19Z","timestamp":1784624659720,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005629","name":"Stiftung Tier\u00e4rztliche Hochschule Hannover","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005629","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Niemann\u2010Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder that affects approximately 1 in 100\u2009000 live births. It is primarily caused by mutations in the\n                    <jats:italic>NPC1<\/jats:italic>\n                    gene, which disrupts intracellular cholesterol transport and leads to lipid accumulation in late endosomes and lysosomes. This results in visceral dysfunction and progressive neurological deterioration. This study investigated the effects of three NPC1 disease\u2010causing mutations (p.I1061T, p.D874V, and p.P1007A) on NPC1 biosynthesis, trafficking of NPC1, and cellular cholesterol levels. By expressing NPC1 mutants and wild\u2010type NPC1 in\n                    <jats:italic>NPC1<\/jats:italic>\n                    knockout Chinese hamster ovary cells (CHO\u2010CT43), we analysed the trafficking patterns using Western blot based on endoglycosidase H sensitivity. We also examined lipid raft distribution and unesterified cholesterol accumulation using flotillin 2, filipin staining, and high\u2010performance liquid chromatography (HPLC). Our findings revealed significant differences in NPC1 mutant expression levels and trafficking patterns, categorizing them into three distinct phenotypes: intracellularly retained, slow\u2010trafficking, and finally wild\u2010type\u2010like mutants. Notably, the variations in NPC1 mutant expression and trafficking patterns in CHO\u2010CT43 cells correlated with alterations in lipid rafts distribution and cellular cholesterol levels. The study demonstrated a clear association between cholesterol accumulation and NPC1 mutant trafficking phenotypes, with the p.I1061T variant exhibiting the most severe biochemical profile and highest cellular cholesterol levels. In conclusion, this study highlights a promising framework for elucidating the genotype\u2013phenotype relationships in NPC and assessing their potential pathogenicity. These findings have significant implications for understanding the molecular mechanisms underlying NPC, and they propose personalized, targeted therapeutic strategies for this devastating disease.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70186","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:00:35Z","timestamp":1776240035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Trafficking Phenotypes of\n                    <scp>NPC1<\/scp>\n                    Mutant Proteins Reveal Distinct Cholesterol Accumulation Profiles"],"prefix":"10.1002","volume":"49","author":[{"given":"Sanaa Abdelmalek","family":"Mahmoud","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AhmedElmontaser","family":"Mergani","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Veterinary Medicine Hannover  Hannover Germany"},{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"von K\u00f6ckritz\u2010Blickwede","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Veterinary Medicine Hannover  Hannover Germany"},{"name":"Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-8425","authenticated-orcid":false,"given":"Hassan Y.","family":"Naim","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220711"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02200-4"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2004.03.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-16"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5323.228"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.3.805"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002184200"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3061"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.08.012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406090200"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.020"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.02.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414024200"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M200203-JLR200"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R200021-JLR200"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41707-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708735200"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.02.009"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.160308"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062101"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505924200"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/320606"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/302620"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/302626"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100531"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030679"}],"container-title":["Journal 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