{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:12Z","timestamp":1792790352604,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Cell Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute on Aging","award":["R01AG074248"],"award-info":[{"award-number":["R01AG074248"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["RF1AG076653"],"award-info":[{"award-number":["RF1AG076653"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["R01AG076653"],"award-info":[{"award-number":["R01AG076653"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["T32AG057468"],"award-info":[{"award-number":["T32AG057468"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Microglia rely on lysosomes to clear phagocytosed material and orchestrate immune responses, but the mechanisms governing glial lysosome diversity and function remain largely undefined. Using high-resolution, high-throughput 3D imaging of mouse brain tissue, we find that glial lysosomes are heterogeneous in size and protease content depending on subcellular location. CD68+ and LAMP1+ vesicles were more numerous in glial processes than cell bodies; process LAMP1+ vesicles carried less protease than cell-body vesicles, but CD68+ protease content did not differ between compartments, revealing at least two lysosomal subpopulations within processes. Loss of Adaptor Protein complex 4 (AP-4) selectively remodels this landscape: it increases CD68+ vesicle number and CD68 enrichment, particularly in processes, without changing protease content, and disrupts the normal cell-body-versus-process pattern in protease- and CD68-enrichment. AP-4 loss also lowers protease content in cell-body LAMP1+ vesicles, mirroring a neuronal phenotype. These results provide the first evidence of glial lysosome heterogeneity and implicate AP-4 in shaping microglial lysosome composition and inflammatory function.<\/jats:p>","DOI":"10.64898\/2026.09.17.752408","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:35:19Z","timestamp":1789749319000},"source":"Crossref","is-referenced-by-count":0,"title":["Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4"],"prefix":"10.64898","author":[{"given":"Elizabeth A.","family":"Somodji","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA"},{"name":"Department of Biological Sciences, College of Liberal Arts and Sciences, University of Illinois Chicago, Chicago, IL 60607, 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