biostudies-literatureNeuman SDNINDS NIH HHSNCI NIH HHSNIH HHSNIGMS NIH HHSBrown University Carney Institute for Brain Science1356-1368https://www.ebi.ac.uk/biostudies/studies/S-EPMC12273619biostudies-literatureUnknown40(7)<h4>Background</h4>Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.<h4>Objective</h4>The objective of this study was to determine tissue-specific and aging-dependent roles for VPS13A and BLTP2 using Drosophila models.<h4>Methods</h4>We generated tissue-specific knockdowns of the VPS13A ortholog (Vps13) and the BLTP2 ortholog (hobbit) in neurons and muscles of Drosophila. We analyzed age-dependent locomotor behavior, neurodegeneration, and synapse development and function.<h4>Results</h4>NeuronMovement disorders : official journal of the Movement Disorder SocietyNeurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters VPS13A and BLTP2.PMC12273619R01NS0781791R01GM155154R01 NS078179R01 GM155154P30 CA014520S10 OD023526P40 OD018537Thakur RSGratz SJO'Connor-Giles KMBashirullah ANeuman SDfalseNeurodegenerative and Neurodevelopmental Roles for Bulk Lipid Transporters VPS13A and BLTP2.<h4>Background</h4>Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.<h4>Objective</h4>The objective of this study was to determine tissue-specific and aging-dependent roles for VPS13A and BLTP2 using Drosophila models.<h4>Methods</h4>We generated tissue-specific knockdowns of the VPS13A ortholog (Vps13) and the BLTP2 ortholog (hobbit) in neurons and muscles of Drosophila. We analyzed age-dependent locomotor behavior, neurodegeneration, and synapse development and function.<h4>Results</h4>Neuron2025-01-01T00:00:00Z2025 Jul2026-03-27T15:21:23.041Z2025-08-23T03:09:07.334ZS-EPMC122736194015253210.1002/mds.30178