{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GPR173 is a highly conserved member of the “super‐conserved receptor expressed in brain” (SREB) family that is widely distributed throughout the central nervous system and peripheral tissues. As the putative receptor for the neuropeptide phoenixin and even for a GnRH metabolite, GPR173 mediates a broad spectrum of physiological functions. In the brain, activation of GPR173 modulates adult neurogenesis, cognitive processes, mitochondrial biogenesis, and aspects of neuroinflammation by engaging canonical cyclic AMP/protein kinase A (PKA)–CREB signaling as well as non‐canonical β‐arrestin pathways (for example, see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In reproductive tissues such as the ovaries, hypothalamus, and even in gonadotropes and granulosa cells, GPR173 has been shown to regulate key gene expression events—including GnRH, kisspeptin, gonadotropin receptors, and steroidogenic as well as folliculogenic factors—that ultimately affect luteinizing hormone release, estrous cyclicity, and oocyte maturation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " Beyond its neuroendocrine roles, activation of GPR173 by phoenixin‐20 also promotes osteoblastic differentiation via p38 MAPK and RUNX2 induction, supports metabolic functions such as adipogenesis and gut hormone regulation, and exerts protective, anti‐inflammatory actions in endothelial and dental pulp cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": " Furthermore, altered GPR173 expression and/or genetic variants have been linked to reproductive dysfunction (such as in polycystic ovarian syndrome and aberrant ovarian cyclicity), autoimmune conditions, and even differences in traditional Chinese medicine (TCM) syndrome classifications pertaining to liver diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": " Collectively, these findings highlight that GPR173 functions as a versatile receptor coupling through multiple downstream pathways (including Gs‐mediated and β‐arrestin–mediated signals) to coordinate neuroendocrine, skeletal, metabolic, inflammatory, and reproductive processes. The availability of novel ligands, inverse agonists, and gene‐silencing strategies underscores the therapeutic potential of targeting GPR173 in a variety of neuropsychiatric, reproductive, and metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "20"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mitsuyuki Matsumoto, Senda Beltaifa, Cynthia Shannon Weickert, et al. 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