biostudies-literatureSardana SDutch Research Council (NWO)2421-2435https://www.ebi.ac.uk/biostudies/studies/S-EPMC10337253biostudies-literatureUnknown22(7)<i>S</i>-Palmitoylation is the covalent attachment of C14:0-C22:0 fatty acids (mainly C16:0 palmitate) to cysteines via thioester bonds. This lipid modification is highly abundant in neurons, where it plays a role in neuronal development and is implicated in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The knowledge of <i>S</i>-palmitoylation in neurodevelopment is limited due to technological challenges in analyzing this highly hydrophobic protein modification. Here, we used two orthogonal methods, acyl-biotin exchange (ABE) and lipid metabolic labeling (LML), to identify <i>S</i>-palmitoylated proteins and sites during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. We identified 2002 putative <i>S</i>-palmitoylaJournal of proteome research<i>S</i>-Palmitoylation during Retinoic Acid-Induced Neuronal Differentiation of SH-SY5Y Neuroblastoma Cells.PMC10337253VI.Veni.202.020Sardana SBaggelaar MPNederstigt AEfalse<i>S</i>-Palmitoylation during Retinoic Acid-Induced Neuronal Differentiation of SH-SY5Y Neuroblastoma Cells.<i>S</i>-Palmitoylation is the covalent attachment of C14:0-C22:0 fatty acids (mainly C16:0 palmitate) to cysteines via thioester bonds. This lipid modification is highly abundant in neurons, where it plays a role in neuronal development and is implicated in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The knowledge of <i>S</i>-palmitoylation in neurodevelopment is limited due to technological challenges in analyzing this highly hydrophobic protein modification. Here, we used two orthogonal methods, acyl-biotin exchange (ABE) and lipid metabolic labeling (LML), to identify <i>S</i>-palmitoylated proteins and sites during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. We identified 2002 putative <i>S</i>-palmitoyla2023-01-01T00:00:00Z2023 Jul2025-04-04T13:51:35.688Z2025-04-04T13:51:35.688ZS-EPMC103372533729493110.1021/acs.jproteome.3c00151