NOL9 (nucleolar protein 9) is a polynucleotide kinase essential for ribosome biogenesis 1. It phosphorylates 5'-hydroxyl groups on single-stranded and double-stranded RNA/DNA substrates and is required for efficient pre-rRNA processing, particularly ITS2 cleavage and maturation of 5.8S and 28S rRNAs 1. NOL9 associates with the endoribonuclease LAS1L to form a catalytic endonuclease-kinase complex that marks ITS2 for degradation 2. This complex is recruited to the rixosome core scaffold, a multi-subunit complex containing PELP1, WDR18, and TEX10 3. NOL9 contains a nucleolar localization sequence responsible for transporting the assembled Las1L-NOL9 complex into the nucleolus 2. Dysregulation of NOL9 has significant disease implications. In hepatocellular carcinoma, NOL9 is upregulated and correlates with poor prognosis, larger tumors, and advanced pathological grades; its expression is epigenetically regulated by DNA methylation 4. NOL9 promotes HCC growth through Wnt/β-catenin pathway activation 4. In acute myeloid leukemia with NPM1 mutations, elevated LAS1-NOL9 levels affect prognosis, and targeting this axis via LAS1 inhibition impairs 28S rRNA maturation and stabilizes p53 5. NOL9 mutations are recurrent in EBV-positive diffuse large B-cell lymphoma 6. A zebrafish nol9 loss-of-function model demonstrates that NOL9 deficiency causes 28S rRNA processing defects, resulting in hypoplastic pancreas/liver and impaired hematopoiesis, establishing it as central to tissue-specific ribosome biogenesis 7.