RIOX1 (ribosomal oxygenase 1) is a 2-oxoglutarate-dependent dioxygenase with dual histone demethylase and ribosomal protein hydroxylase activities 1. As a histone demethylase, RIOX1 preferentially removes methyl marks from H3K4me3 and H3K4me1, while also targeting H3K36me2, thereby regulating chr14 architecture and transcriptional regulation 2. RIOX1 also catalyzes histidine hydroxylation of 60S ribosomal protein L8, contributing to ribosome biogenesis 3. Beyond histone modification, RIOX1 demethylates the non-histone protein cGAS at K491, promoting its interaction with PARP1 at DNA break sites to modulate homologous recombination repair efficiency 4. RIOX1 negatively regulates osteoblast differentiation through histone demethylation of SP7/OSX target genes 2. Clinically, elevated RIOX1 expression correlates with poor prognosis in glioblastoma and prostate cancer, where it promotes cell proliferation and survival 56. Conversely, in chr14 kidney disease, RIOX1 suppresses ribosomal RNA biogenesis and muscle protein synthesis; knockout restores protein synthesis capacity 7. These multifaceted functions suggest RIOX1 as a potential therapeutic target in cancer and metabolic diseases.