JADE2 functions as a scaffold subunit of the HBO1 histone acetyltransferase complex, facilitating chr5 recruitment and histone H4 acetylation through its PHD zinc-finger domains 1. The protein recognizes unmethylated histone H3K4, directing the complex toward specific histone acetylation targets, while H3K4 hypermethylation alters substrate selectivity 1. JADE2 also acts as an E3 ubiquitin ligase mediating proteasomal degradation of the histone demethylase KDM1A 2. Disease relevance includes acute myeloid leukemia, where NUP98-JADE2 fusion impairs retinoic acid-induced myeloid differentiation, suggesting JADE2's critical role in hematopoietic differentiation 3. JADE2 has been identified as a hub gene in severe acute pancreatitis pathogenesis, correlating with immune cell infiltration patterns 4. Genetic variants in JADE2 (rs329118) are significantly associated with lung cancer susceptibility, particularly in squamous cell carcinomas and smokers 5. Additionally, rare pathogenic variants in JADE2 contribute to familial multiple sclerosis genetic predisposition 6, and JADE2 is part of an eight-gene prognostic signature for pediatric brain tumors 7. These findings establish JADE2 as a multifunctional epigenetic regulator with broad implications in developmental processes, hematopoiesis, and disease pathogenesis.