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While its primary role in carbohydrate storage and energy metabolism in the liver and muscle is well characterized, recent research has highlighted critical metabolic and non\u2010metabolic roles for glycogen in the brain. In this review, the emerging roles of glycogen homeostasis in the healthy and diseased brain are discussed with a focus on advancing our understanding of the role of glycogen in the brain. Innovative technologies that have led to novel insights into glycogen functions are detailed. Key insights into how cellular localization impacts neuronal and glial function are discussed. Perturbed glycogen functions are observed in multiple disorders of the brain, including where it serves as a disease driver in the emerging category of neurological glycogen storage diseases (n\u2010GSDs). n\u2010GSDs include Lafora disease (LD), adult polyglucosan body disease (APBD), Cori disease, Glucose transporter type 1 deficiency syndrome (G1D), GSD0b, and late\u2010onset Pompe disease (PD). They are neurogenetic disorders characterized by aberrant glycogen which results in devastating neurological and systemic symptoms. In the most severe cases, rapid neurodegeneration coupled with dementia results in death soon after diagnosis. Finally, we discuss current treatment strategies that are currently being developed and have the potential to be of great benefit to patients with n\u2010GSD. Taken together, novel technologies and biological insights have resulted in a renaissance in brain glycogen that dramatically advanced our understanding of both biology and disease. Future studies are needed to expand our understanding and the multifaceted roles of glycogen and effectively apply these insights to human disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15926-fig-0005-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15926","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T03:14:36Z","timestamp":1691550876000},"page":"728-743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The multifaceted roles of the brain glycogen"],"prefix":"10.1111","volume":"168","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-0400","authenticated-orcid":false,"given":"Kia H.","family":"Markussen","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry College of Medicine, University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6391-4139","authenticated-orcid":false,"given":"Manuela","family":"Corti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Powell Gene Therapy Center College of Medicine, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-1756","authenticated-orcid":false,"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Powell Gene Therapy Center College of Medicine, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7463-3914","authenticated-orcid":false,"given":"Craig W.","family":"Vander\u00a0Kooi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology College of Medicine, University of Florida  Gainesville Florida USA"},{"name":"Center for Advanced Spatial Biomolecule Research University of Florida  Gainesville Florida USA"},{"name":"Lafora Epilepsy Cure Initiative  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-1850","authenticated-orcid":false,"given":"Ramon C.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology College of Medicine, University of Florida  Gainesville Florida USA"},{"name":"Center for Advanced Spatial Biomolecule Research University of Florida  Gainesville Florida USA"},{"name":"Lafora Epilepsy Cure Initiative  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5253-9049","authenticated-orcid":false,"given":"Matthew S.","family":"Gentry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology College of Medicine, University of Florida  Gainesville Florida USA"},{"name":"Center for Advanced Spatial Biomolecule Research University of Florida  Gainesville Florida USA"},{"name":"Lafora Epilepsy Cure Initiative  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"e_1_2_19_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab194"},{"key":"e_1_2_19_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23250"},{"key":"e_1_2_19_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010022\u201003771\u20101"},{"key":"e_1_2_19_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011081"},{"key":"e_1_2_19_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/1971306a0"},{"key":"e_1_2_19_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00396"},{"key":"e_1_2_19_8_1","doi-asserted-by":"publisher","DOI":"10.5357\/koubyou.60.264"},{"issue":"4","key":"e_1_2_19_9_1","first-page":"324","article-title":"Observations concerning vacuolation and deposition of glycogen in nuclei of hepatic cells","volume":"6","author":"Baird W. 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