TRIM49 is an E3 ubiquitin ligase involved in autophagy regulation and cancer suppression. Primary function: TRIM49 regulates ULK1-mediated autophagy initiation and photoreceptor outer segment phagocytosis by retinal pigment epithelium cells 1. The protein contains characteristic TRIM domains (RING, B-box, coiled-coil, and SPRY) and participates in autophagic protein degradation 2. Mechanistically, TRIM49 acts as a tumor suppressor in gastric adenocarcinoma by mediating polyubiquitination and proteasomal degradation of galectin-3, preventing assembly of a pro-invasive galectin-3/EGR1 transcriptional complex 3. Disease relevance: TRIM49 deficiency is associated with aggressive cancer invasiveness and metastasis in gastric adenocarcinoma, where reduced expression correlates with deeper tumor infiltration, lymph node metastasis, and shorter overall survival 3. Biallelic TRIM49 variants cause retinitis pigmentosa through impaired autophagy and retinal pigment epithelium dysfunction 1. TRIM49 variants are also associated with steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus patients 4. Clinical significance: Targeting the galectin-3/EGR1 complex with galectin-3 inhibitors like GB1107 may prevent metastasis in TRIM49-deficient gastric adenocarcinoma, and restoring RPE autophagy through TRIM49 represents a potential therapeutic approach for retinal degenerative diseases.