{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:51:17Z","timestamp":1793069477720,"version":"4.5.0"},"reference-count":115,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Huntingtin (\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    ) is an essential pleiotropic gene. Primarily known for its pathogenic role in Huntington's disease (HD), a progressive autosomal dominant neurodegenerative disorder. HD is caused by a CAG expansion located in\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    exon 1 that produces an altered protein product, mutant huntingtin, with an expanded polyglutamine stretch. Despite its monogenic origin, HD has a complex cellular pathology likely due to huntingtin's many protein-protein interactions and diverse functional roles. Wild-type huntingtin loss-of-function may influence HD pathogenesis by intertwining with multiple forms of mutant huntingtin gain-of-function toxicity. Multiple studies have identified irregular neurodevelopmental phenotypes in HD models similar to those due to wild-type huntingtin loss-of-function. Current huntingtin lowering treatment developments suggest that a better understanding of normal HTT functions may be vital for effective therapeutic development. Due to the history of huntingtin gene discovery, most previous reviews have focused on the wild-type huntingtin allele in the context of also inheriting the mutant huntingtin allele. The purpose of this review is to explore wild-type huntingtin's putative function, expression, and variation in neurodevelopment in the absence of the mutant\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    allele, providing a basis to better understand how changes in wild-type huntingtin function may play a role in human health and disease.\n                  <\/jats:p>","DOI":"10.1177\/18796397251410442","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:18:43Z","timestamp":1775762323000},"page":"252-262","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Wild-type huntingtin in neurodevelopment"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3473-8252","authenticated-orcid":false,"given":"Laura Lynn","family":"Chan","sequence":"first","affiliation":[{"name":"University of British Columbia 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