TPRKB (TP53RK binding protein) is a core component of the EKC/KEOPS complex, a highly conserved five-subunit complex essential for tRNA modification and cellular fitness 1. TPRKB functions as an allosteric effector regulating the complex's catalytic activity in synthesizing N6-threonylcarbamoyl adenosine (t6A) at position 37 of adenine-reading tRNAs 23. The complex transfers the threonylcarbamoyl moiety from threonylcarbamoyl-AMP to the N6 group of A37, a modification critical for translational fidelity 3. TPRKB interacts directly with PRPK, as revealed by crystallographic analysis 4. TPRKB mutations cause Galloway-Mowat syndrome (GAMOS), characterized by early-onset nephrotic syndrome and microcephaly 35. Disease mechanisms include impaired protein translation, endoplasmic reticulum stress, DNA-damage signaling, and apoptosis 3. TPRKB is also implicated in cancer biology: TP53-deficient cancer cells show selective dependence on TPRKB for proliferation, with TP53 indirectly mediating TPRKB degradation 6. In hepatocellular carcinoma, TPRKB is highly expressed and predicts poor outcomes; METTL5-mediated m6A methylation regulates TPRKB mRNA stability 7. These findings establish TPRKB as essential for both normal development and disease pathogenesis.