YRDC is a cytoplasmic and mitochondrial threonylcarbamoyl-AMP synthase that catalyzes formation of the N6-threonylcarbamoyladenosine (t6A) modification at position 37 of tRNAs decoding codons beginning with adenine. The enzyme converts L-threonine, bicarbonate/CO₂, and ATP to generate threonylcarbamoyl-AMP as an intermediate, releasing diphosphate. This t6A modification is essential for translational accuracy and efficiency across both cytoplasmic and mitochondrial tRNA pools. Mutations in YRDC cause an extremely severe form of Galloway-Mowat syndrome, characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly 1. In cancer contexts, YRDC is markedly overexpressed and associated with poor prognosis 2. In glioblastoma stem cells, YRDC emerges as the top essential tRNA modification enzyme; elevated threonine accumulation facilitates t6A formation through YRDC and shifts the proteome toward mitosis-related genes with ANN codon bias 3. YRDC also promotes hepatocellular carcinoma progression via MEK/ERK signaling 4 and drives EGFR-TKI resistance in non-small cell lung cancer through mechanisms involving YRDC mRNA translation control 5. These findings identify YRDC as both a therapeutic target and a prognostic biomarker across multiple cancer types.