REVIEW article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
The Palmitoylation Code in Cell Death Signaling: From Molecular Mechanisms to Therapeutic Opportunities
Provisionally accepted
Han-xi Xiao1,2
Zhou-zhou Li1,2
Xu-huan Li3Ting Chen1,2Xin-rong Tang1,2Yu Zhang1,2
Zu-xiu Wang4*
Yongping Pan1,2*- 1Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- 2Rehabilitation College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- 3Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
- 4Jiangsu Engineering Research Center of Medical Genetics and Transformation, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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The dynamic lipid modification known as protein palmitoylation is essential for modulating protein activity and subcellular distribution. This process is increasingly recognized as a pivotal molecular mechanism governing the balance between cellular survival and death. This paper explores the molecular regulation of palmitoylation within diverse pathways of regulated cell death, for instance, in necroptosis, ferroptosis, pyroptosis, and apoptosis. The core findings indicate that by controlling the stability, membrane anchoring, and interactions of key signaling proteins, palmitoylation can precisely regulate the ultimate fate of the cell. Additionally, the dysregulation of palmitoylation is closely linked to the pathogenesis of major human diseases, including cancer, neurodegenerative disorders, and inflammatory diseases. For instance, the process can display a dual role in tumor progression, acting to either promote or inhibit it. Concurrently, it is essential for the inflammatory signaling in pyroptosis and for mounting a cellular defense against ferroptosis. A deeper understanding of these regulatory networks provides highly promising therapeutic targets for disease intervention. Targeting the activity of specific palmitoylation-related enzymes has emerged as an innovative strategy for developing novel therapies for a range of diseases, demonstrating significant clinical translational potential.
Keywords: Apoptosis, Cancer, Cell Death, ferroptosis, neurodegenerative disease, palmitoylation, programmed cell death, pyroptosis
Received: 06 Nov 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Xiao, Li, Li, Chen, Tang, Zhang, Wang and Pan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zu-xiu Wang
Yongping Pan
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