{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AHCYL1, also known as IRBIT, is a multifunctional regulatory protein with context‐dependent roles in both normal physiology and disease. In normal epithelial cells, AHCYL1/IRBIT modulates intracellular Ca²⁺ signaling by binding to inositol 1,4,5‐trisphosphate receptors and competing with IP₃, thereby fine‐tuning Ca²⁺ release from intracellular stores."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, AHCYL1/IRBIT coordinates epithelial ion and fluid transport by stimulating key transporters – it activates the Na⁺/HCO₃⁻ cotransporter NBCe1‐B, promotes Cl⁻ secretion via the cystic fibrosis transmembrane conductance regulator (CFTR), and facilitates Na⁺/H⁺ exchanger (NHE3) trafficking – thereby regulating cellular pH and bicarbonate/fluid secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, AHCYL1/IRBIT interacts with components of the mRNA 3′‐processing machinery (such as CPSF and poly(A) polymerase) to influence mRNA polyadenylation, and it modulates signaling pathways in neurons by binding to and suppressing CaMKIIα activity, thus impacting catecholamine homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, AHCYL1 plays a dual role. In intrahepatic cholangiocarcinoma, fusion of FGFR2 with AHCYL1 yields an oncogenic driver that activates downstream signaling and confers sensitivity to FGFR inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, altered expression and differential promoter methylation of AHCYL1 have been associated with ovarian carcinogenesis, where its expression appears to correlate with a more favorable prognosis in human epithelial ovarian cancer despite its oncogenic association in some animal models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, diverse cellular functions of AHCYL1/IRBIT are further modulated by its phosphorylation state and interactions with other proteins, including self‐association with AHCY and binding to partners such as galectin‑3, which may influence its subcellular distribution and regulatory capacity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies establish AHCYL1/IRBIT as a key coordinator of intracellular signaling, ion transport, and gene expression whose dysregulation contributes to disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benoit Devogelaere, Nael Nadif Kasri, Rita Derua, et al. 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