TRIM2 is an 81 kDa E3 ubiquitin ligase located at chromosome 4.3 that plays diverse roles in neuroprotection and cellular homeostasis 1. As an E3 ubiquitin ligase, TRIM2 mediates polyubiquitination of multiple substrates including neurofilament light chain (NEFL) and pro-apoptotic proteins. TRIM2 ubiquitinates phosphorylated BCL2L11 and BNIP3, targeting them for proteasomal degradation to inhibit apoptosis 2. Additionally, TRIM2 enhances carnitine palmitoyltransferase 1A (CPT1A) activity independent of its ubiquitin ligase function, promoting fatty acid oxidation during metabolic stress 3. TRIM2 participates in antiviral immunity by limiting New World arenavirus infection and restricts influenza and measles virus replication through autophagy regulation 4. TRIM2 self-associates through its RING domain to achieve catalytic activity, with subtle amino acid variations distinguishing it functionally from paralogous TRIM3 5. Clinically, biallelic TRIM2 mutations cause Charcot-Marie-Tooth disease type 2R, an axonal neuropathy 6. TRIM2 is downregulated in aldosterone-producing adenomas, where its loss contributes to excessive aldosterone synthesis 7. Thus TRIM2 functions as a multifaceted regulator controlling neuronal survival, metabolic adaptation, and immune responses.