PSTK (phosphoseryl-tRNA kinase) is an essential enzyme that specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), serving as a critical intermediate in selenocysteine biosynthesis 1. This kinase shows high specificity, with no detectable activity toward other tRNAs. PSTK functions within the conserved PSTK-SepSecS pathway, where it works upstream of selenocysteinyl-tRNA synthase to enable selenoprotein synthesis 1. The enzyme's mechanism involves phosphorylation of the seryl moiety on tRNA(Sec), which is subsequently converted to selenocysteine by selenocysteinyl-tRNA synthase using selenophosphate as a selenium donor 1. PSTK demonstrates significant clinical relevance across multiple disease contexts. In hepatocellular carcinoma, PSTK suppresses chemotherapy-induced ferroptosis by maintaining GPX4 activity and glutathione metabolism, contributing to drug resistance 2. Similarly, in acute myeloid leukemia, PSTK inhibition triggers a self-reinforcing loop involving cGAS-STING activation and ROS generation, ultimately leading to ferroptotic death of leukemic stem cells 3. PSTK also shows protective effects against cisplatin-induced nephrotoxicity by inhibiting the BAX/BCL2/Caspase3 apoptotic pathway and reducing oxidative stress 4. Additionally, PSTK serves as a potential biomarker for tuberculosis treatment monitoring, with levels increasing during anti-TB therapy 5.