{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies in Drosophila have revealed that the USH gene—whose human homolog is ZFPM2 (also known as FOG2)—plays an essential role in regulating cell‐autonomous growth through inhibition of PI3K activity, thereby affecting overall body size and insulin signaling. In addition, investigations in mammalian systems have shown that FOG2 functions as a transcriptional cofactor with GATA factors to modulate preadipocyte proliferation and differentiation, emphasizing its role in metabolic and cellular growth regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular realm, ZFPM2/FOG2 is integral to cardiac morphogenesis and function. By partnering with GATA4, it orchestrates transcriptional programs essential for the proper development of the heart’s outflow tracts. Mutations or dysregulation of ZFPM2 have been linked to a spectrum of congenital heart defects—including conotruncal anomalies such as tetralogy of Fallot, double outlet right ventricle, and other outflow tract malformations—and may also impair thyroid hormone signaling in the failing heart. Notably, although one study did not identify pathogenic mutations in tricuspid atresia, the preponderance of evidence supports a pathogenic role for ZFPM2 variants in various cardiac disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nZFPM2/FOG2 also plays a crucial role in gonadal and diaphragmatic development. In the developing ovary and in cases of 46,XY disorders of sex development, FOG2 has been shown to interact with GATA factors to ensure normal gonadal differentiation, with mutations leading to gonadal dysgenesis. Furthermore, deleterious variants in ZFPM2 have been identified in patients with congenital diaphragmatic hernia, underscoring its importance in the formation and integrity of the diaphragm. Expression alterations have also been observed in ovarian tumors, suggesting broader roles in reproductive tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "20"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond developmental roles, aberrations involving ZFPM2 contribute to oncogenic processes. In hematologic malignancies, an in‐frame fusion of AML1 with FOG2 has been implicated in myelodysplasia, disrupting normal transcriptional control. In solid tumors, the long noncoding RNA ZFPM2‐AS1 exerts oncogenic effects in lung adenocarcinoma by downregulating ZFPM2, while in gliomas, expression levels and genetic variants of ZFPM2 have been associated with tumor grade and susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "23"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional functions of ZFPM2/FOG2 have been uncovered in diverse regulatory contexts. In hepatocytes, FOG cofactors contribute to modulation of hepcidin expression under inflammatory conditions, while in erythroid cells, alterations in FOG2 levels have been linked to a switch in globin gene transcription. Such findings extend the impact of ZFPM2 from developmental biology into the regulation of differentiated tissue function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seogang Hyun, Jung Hyun Lee, Hua Jin, et al. 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