[The dual roles of UFMylation in immune regulation and tumorigenesis]

UFMylation is a novel ubiquitin-like post-translational modification catalyzed by a three-enzyme cascade comprising E1, E2, and E3. It participates in regulating various biological processes, including endoplasmic reticulum function, DNA damage repair, and erythropoiesis, thereby contributing to the maintenance of cellular homeostasis. Studies demonstrate that UFMylation modulates immune signaling pathways and influences the functions of immune cells such as macrophages and T cells, implicating its role in antiviral immunity and inflammatory responses. In recent years, the involvement of the UFMylation system in cancer has attracted increased attention. On the one hand, it regulates tumor cell-autonomous functions including apoptosis and proliferation through the modification of specific substrates. On the other hand, it shapes the tumor immune microenvironment by targeting immune checkpoints like programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), thereby promoting or suppressing tumor growth. With the continuous identification of novel UFMylation substrates, the functional implications of this modification in immune-related diseases and various types of cancers are being progressively unraveled. This review provides an overview of the UFM1 system and its physiological and pathological functions, with a specific emphasis on its mechanisms and roles in immune regulation and tumor development.