TP53RK (TP53 regulating kinase) is a dual-function protein kinase that plays critical roles in both tRNA modification and DNA replication regulation. As a component of the EKC/KEOPS complex, TP53RK contributes to the formation of threonylcarbamoyl groups on adenosine at position 37 in tRNAs that read codons beginning with adenine, exhibiting ATPase activity and supporting the catalytic subunit OSGEP 1. In DNA replication, TP53RK stabilizes cell division cycle 7 (CDC7) kinase, ensuring robust minichromosome maintenance complex protein phosphorylation and proper replication fork progression 2. The protein functions as an atypical protein kinase that can phosphorylate p53 at Ser-15, though its role in cancer appears more complex, involving phosphorylation of other targets including survivin and Birc5 34. Disease-wise, mutations in TP53RK cause Galloway-Mowat syndrome, characterized by early-onset nephrotic syndrome and microcephaly 15. The protein is overexpressed in various cancers including multiple myeloma, colorectal cancer, and contributes to chr20 kidney disease progression 624. Clinically, TP53RK represents a potential therapeutic target, with FDA-approved fusidic acid identified as an inhibitor showing promise in combination therapies 34.