TRIM46 is a microtubule-associated protein with dual roles in neuronal development and disease pathogenesis. In neurons, TRIM46 organizes parallel microtubule bundles in the proximal axon, essential for axon specification, neuronal polarity establishment, and proper neuronal migration 1. TRIM46 knockout impairs hippocampal architecture, reduces dendritic arbors and spines, and causes hypoactive behavioral changes in rats 1. Mechanistically, TRIM46 functions as an E3 ubiquitin ligase promoting substrate degradation. In diabetic retinopathy, TRIM46 promotes ferroptosis by ubiquitinating GPX4 and IκBα, activating pro-inflammatory NF-κB signaling and reducing retinal capillary endothelial cell viability 23. During H1N1 infection, TRIM46 similarly accelerates ferroptosis and inflammation through SLC7A11 ubiquitination 4. In cancer progression, TRIM46 acts as an oncogene. In lung adenocarcinoma, TRIM46 amplification promotes glycolysis and chemoresistance via PHLPP2 ubiquitination and AKT activation 5. In pancreatic cancer, ONECUT3 transcriptionally upregulates TRIM46 to activate NF-κB signaling, enhancing cell proliferation and invasion 6. TRIM46 also associates with gout susceptibility 7, and autoimmune antibodies against TRIM46 have been identified in cerebellar ataxia patients 8.