{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:39:11Z","timestamp":1772159951117,"version":"3.50.1"},"reference-count":73,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01GM155154"],"award-info":[{"award-number":["1R01GM155154"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS078179"],"award-info":[{"award-number":["R01NS078179"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bridge\u2010like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early\u2010onset neurodevelopmental and later\u2010onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to determine tissue\u2010specific and aging\u2010dependent roles for <jats:italic>VPS13A<\/jats:italic> and <jats:italic>BLTP2<\/jats:italic> using <jats:italic>Drosophila<\/jats:italic> models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated tissue\u2010specific knockdowns of the <jats:italic>VPS13A<\/jats:italic> ortholog (<jats:italic>Vps13<\/jats:italic>) and the <jats:italic>BLTP2<\/jats:italic> ortholog (<jats:italic>hobbit<\/jats:italic>) in neurons and muscles of <jats:italic>Drosophila<\/jats:italic>. We analyzed age\u2010dependent locomotor behavior, neurodegeneration, and synapse development and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neuron\u2010specific loss of the <jats:italic>VPS13A<\/jats:italic> ortholog caused neurodegeneration followed by aging\u2010dependent movement deficits and reduced lifespan, whereas muscle\u2010specific loss affected only lifespan. In contrast, neuronal loss of the <jats:italic>BLTP2<\/jats:italic> ortholog resulted in severe early\u2010onset locomotor defects without neurodegeneration, whereas muscle loss impaired synaptogenesis and neurotransmission at the neuromuscular junction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>VPS13A<\/jats:italic> maintains neuronal survival, whereas <jats:italic>BLTP2<\/jats:italic> orchestrates synaptic development. The phenotypic specificity of BLTP function provides mechanistic insights into distinct disease trajectories for BLTP\u2010associated disorders. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30178","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T19:03:39Z","timestamp":1743361419000},"page":"1356-1368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters <scp><i>VPS13A<\/i><\/scp> and <scp><i>BLTP2<\/i><\/scp>"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5731-6426","authenticated-orcid":false,"given":"Sarah D.","family":"Neuman","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical 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