TRIM41 is an E3 ubiquitin ligase with primary roles in innate antiviral immunity and genome protection. As an intrinsic antiviral restriction factor, TRIM41 directly binds influenza A virus and vesicular stomatitis virus nucleoproteins through its SPRY domain and catalyzes their polyubiquitination, targeting them for proteasomal degradation and limiting viral infection 1. TRIM41 also activates antiviral signaling by monoubiquitinating cGAS, enhancing DNA sensing responses. In genome maintenance, TRIM41 ubiquitinates LINE-1 ORF2p protein; nuclear cGAS enhances this interaction following DNA damage-induced phosphorylation, suppressing L1 retrotransposition and preserving genome integrity 2. TRIM41-mediated cGAS ubiquitination can be weakened by specific amino acid changes, as observed in naked mole-rats, prolonging cGAS chr5 binding and potentiating DNA repair 3. Beyond immune functions, TRIM41 catalyzes degradation of other substrates including GPX4 (regulating ferroptosis) 4, ZSCAN21 (affecting α-synuclein expression in Parkinson's disease pathogenesis) 5, TOP3B (in DNA repair), and p53 (in cancer drug resistance) 6. TRIM41 exists as multiple isoforms localizing to both cytoplasm and nucleus 7, positioning it as a multifunctional regulator linking viral defense, DNA repair, cellular aging, and disease susceptibility.