JMJD6 is a Fe(II)- and 2-oxoglutarate-dependent dioxygenase that functions as both an arginine demethylase and lysyl-hydroxylase, playing critical roles in transcriptional regulation, RNA splicing, and cellular metabolism 1. The protein catalyzes histone arginine demethylation, particularly of H3R2me and H4R3me, and lysine hydroxylation of splicing factors like U2AF65, thereby regulating gene expression and RNA processing 1. JMJD6 demonstrates significant disease relevance across multiple cancer types, where its overexpression correlates with tumor progression and poor prognosis 2. In prostate cancer, SPOP mutations lead to JMJD6 accumulation, which coordinates with ATF4 to enhance glutathione biosynthesis and confer ferroptosis resistance 3. Similarly, in lung cancer, JMJD6 promotes progression through the METTL14/m6A/SLC3A2 axis, though its acetylation at K375 by PCAF restrains this oncogenic function 4. JMJD6 also regulates immune responses, particularly in tumor-associated macrophages where it promotes M2 polarization via the STAT3/IL-10 pathway, contributing to immunosuppression 5. Additionally, JMJD6 participates in antiviral responses by demethylating hnRNPA2B1, facilitating its cytoplasmic translocation and subsequent IFN-α/β production 6. These diverse functions establish JMJD6 as a promising therapeutic target for cancer treatment, with small molecule inhibitors showing potential in preclinical studies.