RIOK1 (RIO kinase 1) is an atypical serine/threonine kinase that functions primarily in ribosomal biogenesis and has emerged as a significant oncogenic driver. In ribosome assembly, RIOK1 is involved in the final cytoplasmic maturation steps of the 40S ribosomal subunit and processing of 18S-E pre-rRNA to mature 18S rRNA 1. The protein acts as an adapter by recruiting nucleolin to the PRMT5 methyltransferase complex, facilitating substrate recognition through a conserved peptide motif shared with other PRMT5 adaptors 21. RIOK1's catalytic activity, functioning predominantly as an ATPase rather than a traditional kinase, regulates its dynamic association with ribosomal subunits 1. In cancer, RIOK1 is overexpressed in hepatocellular carcinoma and colorectal cancer, correlating with poor prognosis 34. Mechanistically, RIOK1 promotes oncogenesis by phosphorylating G3BP2 at Thr226, leading to p53 degradation and radioresistance 4. Additionally, RIOK1 undergoes phase separation to form stress granules that sequester PTEN mRNA, reducing translation and activating protective metabolic pathways against therapeutic stress 5. RIOK1 also contributes to cancer stem cell maintenance and platinum resistance through the SPC25/RIOK1/MYH9 axis, activating Wnt/β-catenin signaling 6. These findings establish RIOK1 as both an essential ribosomal biogenesis factor and a promising therapeutic target in multiple cancers.