Usp12, a member of the ubiquitin-specific proteases family, is a deubiquitinase. Deubiquitination, the process it mediates, counteracts ubiquitination to maintain protein stability and cellular homeostasis. Usp12 is involved in multiple biological processes such as cell proliferation, autophagy, apoptosis, and cell cycle progression, and is associated with various signaling pathways like the STING/TBK-1/IRF3, NF-κB, and Hippo/YAP pathways [1].

Knockout or knockdown of Usp12 has shown diverse effects. In antiviral response, Usp12 deficiency impaired HSV-1-induced expressions of IFN-β, CCL-5, IL-6, and downstream interferon-stimulated genes (ISGs), increased HSV-1 replication, and host susceptibility [2]. In lung cancer, down-regulation of Usp12 promoted tumor growth, fostered an immunosuppressive microenvironment, and enhanced resistance to PD-1 blockade [3]. In gastric cancer, depletion of Usp12 inhibited cancer progression via the Hippo/YAP axis [4]. In non-small cell lung cancer, knockdown of Usp12 caused DNA replication stress and retarded tumor growth [5]. In breast cancer, knockdown of Usp12 decreased lung metastasis ability [6]. In CD4+ T cells, Usp12-deficient cells protected mice from autoimmune diseases but subdued the immune response against bacterial infection [7]. In myeloid-derived suppressor cells (MDSCs), Usp12 deficiency decreased infiltration and impaired suppressor function, decelerating tumor growth [8]. In human periodontal ligament cells under tension stress, knockdown of Usp12 enhanced osteogenesis [9].

In conclusion, Usp12 is crucial for maintaining normal biological functions. Through gene knockout or knockdown models, its roles in antiviral responses, tumorigenesis, immune regulation, and osteogenesis have been revealed. These findings suggest that Usp12 could be a potential target for treating related diseases such as viral infections, various cancers, autoimmune and inflammatory diseases, and for modulating bone remodeling processes.