TRIM50 is an E3 ubiquitin ligase that regulates cellular homeostasis through multiple mechanisms. It ubiquitinates Beclin-1 in a Lys-63-dependent manner, enhancing its interaction with ULK1 and promoting starvation-induced autophagy 1. TRIM50 also interacts with p62 and HDAC6 to facilitate the clearance of polyubiquitinated protein aggregates through the aggresome pathway 2. Beyond autophagy, TRIM50 acts as a tumor suppressor across multiple cancer types. In gastric cancer, TRIM50 is downregulated and inhibits glycolysis by ubiquitinating PGK1, suppressing cell proliferation and M2 polarization of tumor-associated macrophages 3. In triple-negative breast cancer, TRIM50 overexpression reduces proliferation and migration by attenuating epithelial-mesenchymal transition through SNAI1 depletion 4. In ovarian cancer, TRIM50 directly suppresses the Src proto-oncogene by inducing K48-linked polyubiquitination, inhibiting tumor growth 5. Gastric cancer studies additionally show TRIM50 regulates JUP ubiquitination to inhibit MYC signaling 6. Recent evidence suggests that MAZ-mediated m6A methylation of TRIM50 mRNA influences its expression in hepatocellular carcinoma, and dihydroartemisinin upregulates TRIM50 transcription to enhance autophagy-mediated hepatocarcinogenesis suppression 7. TRIM50 emerges as a prognostic marker and potential therapeutic target for multiple cancer types.