RIOX2 (ribosomal oxygenase 2) is a JmjC domain-containing enzyme with dual enzymatic activities 1. It functions as both a histone lysine demethylase, catalyzing demethylation of trimethylated lysine-9 on histone H3 (H3K9me3) to increase ribosomal RNA expression, and a ribosomal histidine hydroxylase that modifies 60S ribosomal protein L27a 2. These modifications suggest involvement in ribosome biogenesis and protein synthesis regulation, potentially supporting cell growth and survival 3. RIOX2 is significantly upregulated in multiple malignancies. In lung cancer, RIOX2 is highly expressed in both adenocarcinoma and squamous cell carcinoma, with expression negatively correlated to promoter methylation 4. High RIOX2 expression predicts poor overall survival in lung squamous cell carcinoma 5. In renal cell carcinoma, elevated RIOX2 expression associates with metastatic progression in clear cell subtype 6. Beyond cancer, RIOX2 has emerged as a candidate autosomal recessive Parkinson's disease gene, identified through analysis of AR-PD families 7, suggesting broader neurological significance. The enzyme's amenability to small-molecule inhibition positions it as a potential therapeutic target in cancer and neurodegenerative diseases 1.