KDM3A (lysine demethylase 3A) is a histone demethylase that specifically removes repressive mono- and di-methyl marks from histone H3 lysine 9 (H3K9me1/me2), thereby promoting transcriptional activation 12. The enzyme functions through α-ketoglutarate-dependent chr2 remodeling mechanisms 3 and plays critical roles in multiple physiological processes. In cancer contexts, KDM3A promotes malignant progression through various pathways: it activates HIF1 signaling in hepatocellular carcinoma 4, suppresses tumor-intrinsic interferon responses in gastric cancer by inhibiting endogenous retroviruses 5, and drives PAX3/FOXO1-dependent and independent gene expression programs in rhabdomyosarcoma 2. KDM3A also contributes to bladder cancer metastasis, where it is regulated by the deubiquitinase USP13 through cytoplasmic degradation 6. In metabolic regulation, KDM3A facilitates adipocyte browning through urea cycle metabolites and fumarate accumulation 7 and enables glucose-responsive adipogenesis via chr2 accessibility changes 3. Additionally, KDM3A participates in vascular injury responses under hyperglycemic and hypoxic conditions through HIF-1α signaling 8 and maintains replication fork stability by enabling dynamic heterochromatin assembly and disassembly 1.