{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZDHHC9 is an integral membrane protein that functions as a palmitoyltransferase, catalyzing the reversible post‐translational modification of protein substrates by attaching palmitate groups. In association with its cofactor GCP16, ZDHHC9 palmitoylates critical signaling molecules such as H‐ and N‐Ras, thereby regulating their membrane localization and downstream oncogenic signaling. This activity is essential for maintaining proper plasma membrane targeting, as illustrated by its role in promoting Ras plasma membrane association in yeast and mammalian models. Moreover, ZDHHC9-mediated palmitoylation extends to other substrates; for example, S-palmitoylation of the glucose transporter GLUT1 is crucial for its plasma membrane distribution and, consequently, for sustaining glycolysis and tumor progression in glioblastoma. Perturbations in ZDHHC9 expression and function have also been observed in gastrointestinal tumors and lung adenocarcinoma where alterations in palmitoylation of targets, including PD-L1, contribute to tumorigenic processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its oncogenic roles, mutations in ZDHHC9 have been implicated in neurodevelopmental disorders. Genetic variants that impair its autopalmitoylation activity lead to a reduction in the steady-state level of the palmitoyl-enzyme intermediate, which is critical for the modification of key neuronal proteins. Patients harboring ZDHHC9 mutations present with intellectual disability, specific deficits in speech and language, and distinctive neuroanatomical alterations such as reduced cortical thickness and compromised white matter connectivity. These findings, including those from studies on Lujan-Fryns syndrome, underscore the importance of ZDHHC9-mediated palmitoylation in establishing proper synaptic function and neuronal network organization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "John T Swarthout, Sandra Lobo, Lynn Farh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M504113200"}], "href": "https://doi.org/10.1074/jbc.M504113200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16000296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16000296"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Mansilla, K Birkenkamp-Demtroder, M Kruhøffer, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Ras localization and cell transformation by evolutionarily conserved palmitoyltransferases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01248-13"}], "href": "https://doi.org/10.1128/MCB.01248-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24248599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24248599"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhenxing Zhang, Xin Li, Fan Yang, et al. 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