ZC3H15 is a highly conserved CCCH-type zinc finger protein with multiple cellular functions centered on protein stability and cell signaling. Mechanistically, ZC3H15 protects DRG1 from proteolytic degradation and stimulates its GTPase activity 12. Beyond DRG1, ZC3H15 regulates protein ubiquitination through distinct mechanisms: it recruits the E3 ligase TRIM56 to ubiquitinate PTEN in lung cancer 3, maintains KEAP1 stability to promote NRF2 degradation under oxidative stress 4, and inhibits CBL-mediated EGFR ubiquitination in glioblastoma 5. ZC3H15 is also subject to histidine methylation by CARNMT1 6 and interacts with telomerase to regulate its subcellular localization and telomere maintenance 7. Clinically, ZC3H15 is significantly overexpressed across multiple cancer types including acute myeloid leukemia, hepatocellular carcinoma, glioblastoma, and non-small cell lung cancer 8953. High ZC3H15 expression independently predicts poor prognosis and survival outcomes 9, correlates with advanced tumor features, and confers cisplatin resistance 3. ZC3H15 activates pro-tumorigenic pathways including NFκB 109, AKT-mTOR 3, and EGFR signaling 5. Additionally, ZC3H15 suppression alleviates cancer-induced bone pain by reducing neuronal oxidative stress and microglial inflammation 4, suggesting therapeutic potential beyond tumor control.