biostudies-literatureKalimuthu BU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)U.S. Department of Health & Human Services | NIH | National Institute on AgingU.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentU.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases1-15https://www.ebi.ac.uk/biostudies/studies/S-EPMC12700795biostudies-literatureUnknown31(1)Neurons heavily depend on the ability of the secretory pathway to deliver correctly folded polypeptides to the periphery of the cell for the assembly, maintenance, and normal functioning of synapses. The endoplasmic reticulum (ER) acetylation machinery has emerged as a novel branch of the more general ER quality control machinery. It regulates the positive selection of correctly folded nascent glycoproteins, thus ensuring the efficiency of the conventional secretory pathway. ER acetylation requires the activity of two ER-luminal acetylCoA:lysine acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Both acetyltransferases depend on the influx of acetyl-CoA into the ER from the cytosol, which is ensured by the coordinated action of the citrate transporters, SLC25A1 and SLC13A5, and the ER acetyMolecular psychiatryIncreased expression of ATase1/NAT8B or ATase2/NAT8 in the mouse results in an autistic-like phenotype with altered dendritic branching and spine formation.PMC12700795R01DK071801R01AG052324R01GM148487R01HD064743U54 HD105353R01NS094154R01AG078794P41GM108538Endresen APuglielli LLu HChang QSteenhagen AKalimuthu BRigby MJDong QGray MLi LfalseIncreased expression of ATase1/NAT8B or ATase2/NAT8 in the mouse results in an autistic-like phenotype with altered dendritic branching and spine formation.Neurons heavily depend on the ability of the secretory pathway to deliver correctly folded polypeptides to the periphery of the cell for the assembly, maintenance, and normal functioning of synapses. The endoplasmic reticulum (ER) acetylation machinery has emerged as a novel branch of the more general ER quality control machinery. It regulates the positive selection of correctly folded nascent glycoproteins, thus ensuring the efficiency of the conventional secretory pathway. ER acetylation requires the activity of two ER-luminal acetylCoA:lysine acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Both acetyltransferases depend on the influx of acetyl-CoA into the ER from the cytosol, which is ensured by the coordinated action of the citrate transporters, SLC25A1 and SLC13A5, and the ER acety2026-01-01T00:00:00Z2026 Jan2026-06-06T02:08:21.083Z2026-05-24T03:12:24.531ZS-EPMC127007954099334010.1038/s41380-025-03228-1