ARID5B is a transcription coactivator that binds AT-rich DNA sequences and plays crucial roles in metabolic and hematopoietic development. Mechanistically, ARID5B forms complexes with PHF2 to mediate histone H3K9me2 demethylation at target promoters, facilitating transcription activation 1. It acts as a coactivator of HNF4A in liver development and regulates adipogenesis by controlling adipogenic gene expression and triglyceride metabolism 1. At the molecular level, ARID5B functions as a repressor of preadipocyte enhancers; obesity-associated variants disrupting ARID5B binding motifs lead to derepression of IRX3/IRX5, shifting development from thermogenic beige adipocytes to energy-storing white adipocytes 1. Clinically, ARID5B variants are significantly associated with childhood acute lymphoblastic leukemia (ALL) susceptibility, particularly B-cell ALL, across multiple populations 23. Specific polymorphisms (rs10821936, rs10994982, rs7089424) show ethnicity-dependent associations with ALL risk 2. The rs10821936 C allele correlates with MTX resistance in ALL children and increased disease risk stratification 43. Additionally, ARID5B mutations appear in endometrial carcinomas and HPV-independent cervical cancers 56, and ARID5B is listed among cancer driver genes 7. ARID5B polymorphisms also associate with juvenile systemic lupus erythematosus susceptibility 8.