REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1593394
This article is part of the Research TopicThe Molecular Mechanisms and Therapeutic Implications of Protein Kinase Inhibitors in Cancer TherapyView all 7 articles
Death-Associated Protein Kinase 1 (DAPK1): A Double-Edged Sword in Health and Disease
Provisionally accepted
- 1Fujian University of Traditional Chinese Medicine, Fuzhou, China
- 2Technion Israel Institute of Technology, Haifa, Haifa, Israel
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Death-associated protein kinase 1 (DAPK1) is a Ca 2+ /calmodulin-regulated serine/threonine kinase that orchestrates a wide array of cellular activities. It is intricately regulated through multiple mechanisms, including intramolecular signaling and interactions with other proteins, such as kinases and phosphatases. DAPK1 plays a pivotal role in regulating various biological processes, including apoptosis and autophagy, and is implicated in the pathogenesis of several disorders, such as cancer, stroke and brain damage, neurodegenerative diseases, cardiovascular diseases, wound healing, kidney injury, and tuberous sclerosis complex. In light of its biological significance, several small molecule modulators of DAPK1 have been developed for therapeutic purposes and as probe compounds to enhance the mechanistic understanding of DAPK1-mediated biological functions. However, the repertoire of available small molecules remains limited, underscoring the need for further research to discover novel strategies for the activation or inhibition of DAPK1. From this perspective, we primarily discuss the structure, biological function, and role of DAPK1 in health and disease, as well as the recently identified small molecule inhibitors and activators. This analysis offers valuable insights for advancing research in the DAPK1 field.
Keywords: DAPk1, Biological Processes, small molecule, guardians of inflammation, Health
Received: 14 Mar 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Lin, Zhang and Assaraf. 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:
Yao Lin, Fujian University of Traditional Chinese Medicine, Fuzhou, China
Yehuda G Assaraf, Technion Israel Institute of Technology, Haifa, 3200003, Haifa, Israel
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.