TARBP1 (tRNA guanosine 2'-O-methyltransferase) is a tRNA methyltransferase that selectively methylates tRNA, particularly at the Gm18 position, to stabilize specific tRNA species 1. While originally characterized for its role in HIV-1 TAR RNA binding, competing with RNA polymerase II for TAR binding 234, TARBP1's primary documented function involves tRNA modification and regulation of protein synthesis. TARBP1 is significantly amplified and overexpressed across multiple cancer types. In hepatocellular carcinoma (HCC), TARBP1 overexpression is detected in 61.1% of patients and is an independent prognostic factor associated with decreased overall survival 5. Similarly, in non-small-cell lung cancer, TARBP1 is upregulated in 76.67% of samples and correlates with poor prognosis 6. Mechanistically, TARBP1 promotes cancer progression by facilitating glutamine metabolism: it stabilizes tRNAs required for efficient translation of the glutamine transporter ASCT2, enhancing glutamine uptake to fuel cancer cell growth 1. TARBP1 is also dysregulated in epithelial skin cancers as part of broader microRNA pathway disruption 7, and emerging evidence suggests potential roles in Sjögren's syndrome and Alzheimer's disease susceptibility 89. These findings position TARBP1 as both a cancer biomarker and potential therapeutic target.