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We employed a \u2018proximity labeling\u2019 approach using a biotin ligase, TurboID, for mapping protein\u2013protein interactions in live mammalian cells. We discovered novel TREM2-proximal proteins with diverse functions, including those localized to the Mitochondria-ER contact sites (MERCs), a dynamic subcellular \u2018hub\u2019 implicated in a number of crucial cell physiology such as lipid metabolism. TREM2 deficiency alters the thickness (inter-organelle distance) of MERCs, a structural parameter of metabolic state, in microglia derived from human induced pluripotent stem cells. Our TurboID-based TREM2 interactome study suggest novel roles for TREM2 in the structural plasticity of the MERCs, raising the possibility that dysregulation of MERC-related TREM2 functions contribute to AD pathobiology.<\/jats:p>","DOI":"10.1101\/2023.03.21.533722","type":"posted-content","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T19:00:11Z","timestamp":1679684411000},"source":"Crossref","is-referenced-by-count":1,"title":["Proximity Proteome Analysis Reveals Novel TREM2 Interactors in the ER-Mitochondria Interface of Human Microglia"],"prefix":"10.64898","author":[{"given":"Chulhwan","family":"Kwak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina M.","family":"Finan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu 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