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Mutations in G\u03b25 have been implicated in a multisystem developmental disorder. While the regulation of GPCR signaling at the plasma membrane is likely important in this process, G\u03b25\/R7-RGS also localizes to the cytosol and nucleus. Potential protein\u2013protein interactions of G\u03b25 in these subcellular compartments are not well studied, so we sought to characterize the interactome of G\u03b25 utilizing a live-cell biotin proximity-labeling assay in Neuro-2a cells coupled with mass spectrometry to identify novel protein interactions of the complex. We identified 48 potential interactors of G\u03b25 with two analysis methods, most of which are previously unreported interactions important in neuronal development and function. The enriched phenotypes associated with the G\u03b25 interactome in our results align with previously reported phenotypes of G\u03b25 deficiencies.<\/jats:p>","DOI":"10.1021\/acsomega.6c05064","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:01:29Z","timestamp":1789372889000},"page":"57183-57196","source":"Crossref","is-referenced-by-count":0,"title":["Identification\nof G\u03b25 Interactome Associated\nwith Neuronal Development in Neuro-2a Cells through miniTurbo Proximity\nLabeling"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4191-8905","authenticated-orcid":true,"given":"Harrison J.","family":"McNabb","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor P.","family":"Jewell","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892-0001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Yang","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892-0001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1245-1338","authenticated-orcid":true,"given":"Lisa M.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"National Cancer Institute, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892-0001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-706X","authenticated-orcid":true,"given":"William F.","family":"Simonds","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , , , ,","place":["Bethesda, Maryland, United States, 20892"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"issue":"52","key":"2026092911094871400_cit1","doi-asserted-by":"publisher","first-page":"41100","DOI":"10.1074\/jbc.M110.163600","article-title":"A conserved\nprotein interaction interface on the type 5 G protein beta subunit\ncontrols proteolytic stability and activity of R7 family regulator\nof G protein signaling proteins","volume":"285","author":"Porter","year":"2010","journal-title":"J. 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Lipidol."},{"issue":"8","key":"2026092911094871400_cit52","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1194\/jlr.M026823","article-title":"ACAT2 and ABCG5\/G8\nare both required for efficient\ncholesterol absorption in mice: evidence from thoracic lymph duct\ncannulation","volume":"53","author":"Nguyen","year":"2012","journal-title":"J. Lipid Res."},{"issue":"6","key":"2026092911094871400_cit53","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1194\/jlr.M024356","article-title":"Tissue-specific\nknockouts of ACAT2 reveal that intestinal\ndepletion is sufficient to prevent diet-induced cholesterol accumulation\nin the liver and blood","volume":"53","author":"Zhang","year":"2012","journal-title":"J. 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