USP27X is an X-linked deubiquitinase with dual roles in innate immunity and protein stability regulation. In antiviral responses, USP27X positively regulates the cGAS-STING pathway by catalyzing K48-linked deubiquitination of cGAS, promoting its stabilization 1. Conversely, it negatively regulates RIG-I through K63-linked deubiquitination, thereby inhibiting type I interferon signaling 2. USP27X also regulates K63-linked ubiquitination of MDA5/IFIH1 2. Beyond immunity, USP27X stabilizes pro-apoptotic proteins including BCL2L11/BIM and cFLIP, enhancing death receptor-induced apoptosis through interactions with E3 ligases 3. In cancer contexts, USP27X exhibits oncogenic functions: phosphorylation by PIM2 or GSK3β enhances its deubiquitinase activity toward MYC and CBX2, promoting cancer cell proliferation and chemoresistance 45. USP27X also stabilizes Snail1 in TGFβ-induced epithelial-mesenchymal transition, facilitating tumor invasion 6. Clinically, USP27X mutations cause X-linked intellectual developmental disorder-105 (XLID-105), characterized by developmental delay, intellectual disability, autism spectrum features, and anxiety 78. Pathogenic variants disrupt protein expression and deubiquitinase activity, impairing neural development 9. USP27X represents both an important immune regulator and a therapeutic target in cancer and neurodevelopmental disorders.