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N\u2010myristoylation, catalyzed by NMT1\/2, irreversibly attaches myristic acid to N\u2010terminal glycine residues, enabling stable membrane localization and crosstalk with other post\u2010translational modifications. This review traces NMT research from structural characterization to substrate profiling, highlighting the ordered double\u2010substitution catalytic mechanism and variations in substrate recognition. While prior reviews have covered NMT biochemistry and innate immunity, we emphasize underappreciated roles of N\u2010myristoylation in metabolic vulnerability, immune evasion, and acquired resistance to targeted therapies and immunotherapies. We discuss how exogenous myristic acid from dietary sources fuels oncogenic signaling, and how N\u2010myristoylation regulates key signaling pathways (PI3K\/AKT, MAPK, ferroptosis) and targets (Src, AMPK, EZH2) to drive immunosuppressive and pro\u2010tumor phenotypes. Antitumor potential of NMT inhibitors (e.g., B\u201013, Zelenirstat) and allosteric ABL1 inhibitors (asciminib) is evaluated. Recent methodological advances (including metabolic labeling, click chemistry, spatial proteomics, and computational simulations) are reviewed. However, translational challenges such as biomarker absence, blood\u2013brain barrier limitations, and functional redundancy remain. Addressing these will require combination therapies tailored to specific mutational, metabolic, and immune profiles. In summary, N\u2010myristoylation integrates signaling, metabolism, and immunity, offering a rationale for future precision oncology.<\/jats:p>","DOI":"10.1002\/med.70102","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:21:26Z","timestamp":1788776486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N\u2010Myristoylation: A Central Hub Integrating Tumor Signaling, Metabolism, and Immunity for Precision Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-5693","authenticated-orcid":false,"given":"Deqian","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Dalian Medical University Dalian Liaoning 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