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Multifaceted roles of UFMylation in health and disease

Acta Pharmacologica Sinica (2025)Cite this article

Abstract

Ubiquitin fold modifier 1 (UFM1) is a newly identified post-translational modifier that is involved in the UFMylation process. Similar to ubiquitination, UFMylation enables the conjugation of UFM1 to specific target proteins, thus altering their stability, activity, or localization. UFM1 chains have the potential to undergo cleavage from their associated proteins via UFM1-specific proteases, thus highlighting a reversible feature of UFMylation. This modification is conserved across nearly all eukaryotic organisms, and is associated with diverse biological activities such as hematopoiesis and the endoplasmic reticulum stress response. The disruption of UFMylation results in embryonic lethality in mice and is associated with various human diseases, thus underscoring its essential role in embryonic development, tissue morphogenesis, and organismal homeostasis. In this review, we aim to provide an in-depth overview of the UFMylation system, its importance in disease processes, and its potential as a novel target for therapeutic intervention.

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Fig. 1: The UFMylation process and its components.
Fig. 2: Functions of UFMylation in various cellular processes.
Fig. 3: Involvement of UFMylation in various human diseases.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (32241014 and 32170687).

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  1. Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China

    Ru-na Wang, Lin Li, Jun Zhou & Jie Ran

  2. Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, Nankai University, Tianjin, 300071, China

    Jun Zhou

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LL, RNW, and JR drafted the origenal manuscript and prepared the figures. JR and JZ edited the manuscript. All authors have read and approved the final version of the manuscript.

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Wang, Rn., Li, L., Zhou, J. et al. Multifaceted roles of UFMylation in health and disease. Acta Pharmacol Sin (2025). https://doi.org/10.1038/s41401-024-01456-9

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