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Here, we characterised the axonal transport dynamics of LAMP1- and LAMP2A-positive compartments in human induced pluripotent stem cell (hiPSC)-derived cortical neurons. We found that LAMP1-positive organelles move slower in the retrograde direction, pause more frequently, and display a broader anterograde velocity distribution than LAMP2A-positive vesicles, indicating distinct trafficking behaviours. Co-transport analysis revealed that \u223c65% of motile LAMP1-positive organelles carry LAMP2A, and vice versa, with higher co-transport in the retrograde direction. To explore molecular differences underlying these behaviours, we performed proximity labelling using full-length LAMP1 or LAMP2A fused to the light-activated biotin ligase LOV-Turbo. This approach revealed largely overlapping interactomes, with LAMP2A-associated proteins forming a subset of the LAMP1 interactome and showing an enrichment for synaptic vesicle-related proteins. We further validated ZFYVE16 as a novel interactor of both compartments. Together, our findings indicate that LAMP1- and LAMP2A-positive organelles share overlapping molecular identities but represent functionally distinct axonal populations with divergent transport dynamics.<\/jats:p>","DOI":"10.1242\/jcs.264466","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:38:52Z","timestamp":1768469932000},"source":"Crossref","is-referenced-by-count":6,"title":["LAMP1 and LAMP2A localise to axonal organelles with distinct motility dynamics and partially overlapping molecular signatures in human neurons"],"prefix":"10.1242","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-2599","authenticated-orcid":false,"given":"Reem","family":"Abouward","sequence":"first","affiliation":[{"name":"UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London 1 Department of Neuromuscular Diseases and , London WC1N 3BG ,","place":["UK"]},{"name":"UK Dementia Research 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Neurology, University College London 1 Department of Neuromuscular Diseases and , London WC1N 3BG ,","place":["UK"]},{"name":"The Francis Crick Institute 4 , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9091-8242","authenticated-orcid":false,"given":"Song-Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"DGIST 5 Department of New Biology , , Daegu 42988,","place":["Republic of Korea"]},{"name":"New Biology Research Center, DGIST 6 , Daegu 42988 ,","place":["Republic of Korea"]},{"name":"Stanford University 7 Department of Genetics , , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1746-1339","authenticated-orcid":false,"given":"Fairouz","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute 4 , London NW1 1AT 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