TRIM44 is a tripartite motif-containing ubiquitin ligase with context-dependent roles in cellular regulation and disease. Functionally, TRIM44 acts as a negative regulator of PAX6 expression and modulates protein stabilization through K48-linked ubiquitination 1. In DNA damage response, TRIM44 serves as a critical mediator that recruits the MRN complex to damaged chr11 and regulates the ubiquitination-PARylation balance of PARP1, facilitating homologous recombination repair 2. TRIM44 promotes autophagy by inhibiting autophagy suppression, with cardiac-specific knockout blocking the AKT/mTOR pathway and attenuating pathological cardiac remodeling 3. In cancer progression, TRIM44 exhibits dual roles: it promotes non-small cell lung cancer and esophageal cancer migration/invasion via NF-κB pathway activation 45, and enhances diffuse large B cell lymphoma chemoresistance through autophagy activation 6. Conversely, TRIM44 functions as a tumor suppressor in renal cell carcinoma by promoting K48-linked ubiquitination and proteasomal degradation of vimentin 7. In cardiac fibrosis following myocardial infarction, TRIM44 reduction promotes fibroblast autophagy, suggesting context-dependent regulatory mechanisms 8. TRIM44 dysregulation is associated with Aniridia 3 and represents a potential therapeutic target across multiple disease contexts.