TRIM23 is a multifunctional innate immune regulator with both E3 ubiquitin ligase and GTPase activities that mediates antiviral defense through selective autophagy. Mechanistically, TRIM23 functions within the cGAS-STING-TBK1-TRIM23 axis, where TBK1-mediated phosphorylation at S39 triggers TRIM23 autoubiquitination and GTPase activation, ultimately promoting autophagy-dependent viral restriction 1. TRIM23 catalyzes K27-linked auto-ubiquitination of its ARF domain to activate TBK1, facilitating its dimerization and phosphorylation of the selective autophagy receptor p62, establishing the TRIM23-TBK1-p62 axis as critical for restricting multiple viruses including HSV-1, EMCV, and IAV 2. Beyond antiviral immunity, TRIM23 mediates K63-linked polyubiquitination of HAX1 during energy stress, promoting P-body formation and global translation inhibition 3. Clinically, TRIM23 dysregulation correlates with poor cancer prognosis: elevated expression predicts worse outcomes in gastric cancer and lung adenocarcinoma [PMID:30477642; 45], and promotes chemotherapy resistance in colorectal cancer through GALNT4 upregulation and glucose metabolism dysregulation 5. These findings identify TRIM23 as both a critical antiviral effector and an oncogenic driver warranting therapeutic investigation.