{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Inhibin βC (INHBC) is a member of the transforming growth factor–β superfamily that appears to play multifaceted roles in human physiology and disease. Genetic studies have implicated variants in the INHBC region in the control of serum urate levels and gout risk, suggesting an influence on metabolic regulation and uric acid homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In skeletal muscle, fine‐mapping within the TGF–β pathway has identified INHBC—alongside activin receptor components—as a candidate modulator of myostatin signaling and muscle strength."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " INHBC is also expressed in reproductive tissues; its robust expression in normal endometrium and placenta, as well as its altered expression in various endometrial carcinomas, supports a role in paracrine/autocrine signaling that may affect hormone‐dependent cellular differentiation and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": " In oncology, genetic variation in INHBC has been linked to an increased risk of brain metastasis in non–small cell lung cancer, and upregulation of INHBC via exosomal long noncoding RNAs in colorectal cancer appears to impair natural killer cell–mediated immunity, thereby promoting tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, in the context of diabetic nephropathy, elevated INHBC expression is associated with a proinflammatory cytokine profile, reduced apoptosis, and increased renal cell proliferation, indicating a potential contribution to disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In livestock, INHBC has also emerged as a candidate gene influencing composite reproductive traits, underscoring its importance in fertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Cloning studies reveal that INHBC is predominantly expressed in the liver"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", and regulatory analyses indicate that its expression can be modulated by diverse pathways—including Hedgehog and thyroid hormone signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "—reflecting the complex control of its multifarious functions. Collectively, these findings suggest that INHBC is involved in metabolic regulation, muscle function, reproductive tissue homeostasis, cancer progression, and diabetic complications.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qiong Yang, Anna Köttgen, Abbas Dehghan, et al. 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