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Palmitoylation: an emerging therapeutic target bridging physiology and disease

Weini Li, Jie Shen, Aojia Zhuang, Ruiheng Wang, Qin Li, Anas Rabata, Yanan Zhang, Duo‐Yao Cao

2025Cellular & Molecular Biology Letters16 citationsDOIOpen Access PDF

Abstract

Palmitoylation is a reversible post-translational lipid modification of proteins, catalyzed by the Zinc finger DHHC domain-containing (ZDHHC) family of palmitoyltransferases. Palmitoylation plays a pivotal role in regulating localization, stability, trafficking, and interactions, thereby contributing to a wide range of cellular processes. Dysregulation of palmitoylation has been implicated in numerous pathological conditions, including metabolic disorders, muscular diseases, mitochondrial disorders, cancer, and neurodegeneration. In this review, we summarize recent advances in understanding S-palmitoylation, emphasizing its critical roles in protein regulation, cellular and physiological processes, and its implications in both health and disease. Additionally, we highlight emerging therapeutic opportunities and novel strategies in therapeutic applications targeting this lipid modification.

Topics & Concepts

PalmitoylationNeurodegenerationBiologyNeuroscienceAutophagyCell biologyDiseaseBioinformaticsMedicineBiochemistryPathologyApoptosisCysteineEnzymeMitochondrial Function and PathologyUbiquitin and proteasome pathwaysATP Synthase and ATPases Research