CTU1 (cytosolic thiouridylase subunit 1) catalyzes 2-thiolation of mcm5s2U at wobble position 34 of specific tRNAs (tRNA-Lys, tRNA-Glu, tRNA-Gln), a modification essential for accurate codon decoding during translation 1. As part of the cytosolic thiouridylase complex with CTU2, CTU1 directly binds tRNAs and likely catalyzes adenylation as an intermediate step in the thiolation pathway 1. This tRNA modification mechanism has significant disease relevance in cancer biology. CTU1 expression increases in response to BRAF V600E oncogenic signaling and PI3K pathway activation in melanoma; simultaneous MAPK and CTU1 inhibition synergistically kills melanoma cells by disrupting codon-dependent translation of HIF1A mRNA and reducing glycolysis 2. Similarly, in breast cancer, CTU1 and its partner ELP3 support invasion and metastasis through selective translation of the oncoprotein DEK and downstream LEF1 expression 3. CTU1 is also essential when mTORC1 is inactive, becoming critically required for ribosomal protein synthesis and cell survival 4. Beyond cancer, CTU1 is essential for normal angiogenesis and embryonic development in vertebrates, with CTU1 deficiency causing impaired endothelial cell proliferation and migration 1. These findings establish CTU1 as a potential therapeutic target in both cancer and developmental contexts.