{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARID5B is emerging as a multifunctional transcriptional regulator with critical roles in diverse biological processes and disease states. In adipocyte precursors, ARID5B normally acts as a repressor, and disruption of a conserved ARID5B binding motif by the obesity‐risk rs1421085 variant (located in the FTO region) leads to derepression of a potent preadipocyte enhancer that drives increased expression of IRX3/IRX5. This shift favors a developmental change from energy‐dissipating beige adipocytes toward energy‐storing white adipocytes, with marked reductions in mitochondrial thermogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pediatric acute lymphoblastic leukemia (ALL), multiple genome‐wide association studies have consistently identified common ARID5B polymorphisms that strongly influence disease susceptibility—particularly for B‐cell precursor ALL with hyperdiploidy—and have been linked to variations in treatment outcome. Such findings have been replicated in diverse populations, underscoring ARID5B’s role as a low‐penetrance risk locus in childhood ALL."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Epigenetic studies have further associated differential methylation of ARID5B in cord blood with altered birth weight, with ARID5B knockout mice displaying reduced adipose tissue and lower postnatal weight—suggesting a role in fetal growth and adipose tissue development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n ARID5B also contributes to skeletal development. It functions as a transcriptional co‐regulator in chondrogenesis by physically interacting with Sox9 and recruiting histone demethylases to remove repressive H3K9me2 marks from Sox9 target gene promoters. This epigenetic regulation is essential for normal chondrocyte differentiation and endochondral ossification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ARID5B expression in CD14+ monocytes has been implicated in the modulation of inflammatory and lipid metabolism pathways that promote atherosclerotic burden. Specifically, decreased methylation at an ARID5B enhancer is correlated with increased ARID5B expression and a higher risk of atherosclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, ARID5B has been identified as one of the targets of oncogenic signaling in gastric cancer, where its deregulated expression is linked to increased cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight ARID5B as a pivotal regulator of cell differentiation and metabolic programming. Its genetic and epigenetic variations contribute not only to normal developmental processes—such as adipogenesis and chondrogenesis—but also to disease susceptibilities, including obesity, childhood ALL, and atherosclerosis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Melina Claussnitzer, Simon N Dankel, Kyoung-Han Kim, et al. 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