CTU2 (cytosolic thiouridylase subunit 2) is an essential enzyme that catalyzes the thiolation modification of wobble uridine 34 (U34) in specific tRNAs, including tRNA-Lys, tRNA-Glu, and tRNA-Gln 1. CTU2 forms a functional complex with CTU1 to perform this critical tRNA modification, which is required for accurate codon-anticodon interactions during protein translation 1. The enzyme contains a [4Fe-4S] cluster that is essential for its catalytic activity, with three conserved cysteines coordinating the cluster 2. Functionally, CTU2-mediated tRNA modifications regulate translation of specific mRNAs, including HIF1A, thereby influencing cellular metabolism and glycolysis 3. Disease-wise, biallelic CTU2 variants cause DREAM-PL syndrome, characterized by microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia 1. In cancer, CTU2 is overexpressed across multiple tumor types and promotes oncogenesis through codon-specific translation reprogramming 34. CTU2 expression correlates with therapy resistance in melanoma and poor prognosis in various cancers, making it a potential therapeutic target and biomarker 345. The enzyme's role in immune microenvironment modulation further emphasizes its clinical significance in cancer immunotherapy 4.