KDM6A encodes a histone H3K27 demethylase that plays crucial roles in chrX regulation and tumor suppression. The protein specifically removes di- and trimethyl marks from histone H3 lysine 27 (H3K27me2/3), leading to chrX activation and gene expression changes 12. Beyond its enzymatic activity, KDM6A functions through phase separation, forming liquid condensates via its intrinsically disordered region that are essential for tumor suppression and recruitment of the histone methyltransferase MLL4 3. KDM6A acts as a tumor suppressor in multiple cancers, including bladder cancer where it inhibits metastasis through the ARHGDIB-Rac1 pathway 1, and small cell lung cancer where it regulates subtype plasticity between ASCL1 and NEUROD1 states 4. The gene also mediates oxygen-independent regulation of ferroptosis by controlling lipid metabolic enzymes ACSL4 and ETNK1 2. Clinically, KDM6A mutations cause Kabuki syndrome 2, a rare developmental disorder characterized by intellectual disability, hypotonia, and distinctive facial features 56. KDM6A is frequently mutated across various cancer types, making it an important therapeutic target 7.