NSUN4 is a mitochondrial RNA cytosine methyltransferase that catalyzes 5-methylcytosine (m5C) modification of various RNAs including mitochondrial rRNAs, mRNAs, and long non-coding RNAs 1. The enzyme plays a crucial role in mitochondrial ribosome biogenesis by methylating 12S rRNA in the small subunit, functioning independently of MTERFD2/MTERF4 1. NSUN4 also regulates innate immunity by marking mitochondrial double-stranded RNAs for degradation through m5C modification, particularly targeting light-strand lncRNA termini 1. The m5C-modified RNAs are recognized by C1QBP, which recruits degradation machinery to promote RNA turnover and cytosolic release 1. In cancer contexts, NSUN4 demonstrates significant oncogenic properties across multiple tumor types. It promotes glioma progression by stabilizing CDC42 mRNA through m5C-mediated ALYREF binding, activating PI3K-AKT signaling 2. In lung cancers, NSUN4 enhances circular RNA nuclear export and regulates mitochondrial energy metabolism 34. Clinically, NSUN4 overexpression correlates with poor prognosis in hepatocellular carcinoma and serves as an independent prognostic marker 5. Mendelian randomization studies suggest potential causal relationships between NSUN4 expression levels and breast/prostate cancer risks 6.