{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent epigenetic studies in cancer have implicated aberrations in the NPBWR1 gene. In non‐small‐cell lung cancer and prostate cancer, for example, DNA methylation screening efforts have led to the identification of potential methylation markers that may include NPBWR1, offering promise as biomarkers to guide therapeutic decisions in these malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe discovery of neuropeptides B and W as endogenous ligands for the receptor now known as NPBWR1 (formerly GPR7) has been instrumental in elucidating its biological function in the central nervous system. Expression studies and ligand‐binding assays have localized these interactions predominantly to brain regions such as the hypothalamus, hippocampus, and other limbic structures, supporting a role in neuroendocrine regulation and pain modulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional investigations have revealed that activation of NPBWR1 by neuropeptides B and W triggers key intracellular signaling cascades. In the human adrenal cortex, these events include both adenylate cyclase/PKA and phospholipase C/PKC pathways that stimulate cortisol secretion, while studies in peripheral nerves demonstrate increased receptor expression in myelin-forming Schwann cells under inflammatory conditions—suggesting an involvement in pain transmission and immune-mediated neuropathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variations in NPBWR1 also appear to modulate its physiological roles. A naturally occurring single nucleotide polymorphism resulting in a Y135F amino acid substitution has been associated with altered emotional responses to social cues—as demonstrated by differences in perceived facial expressions—underscoring the receptor’s contribution to social and emotional behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles, NPBWR1 signaling has further been implicated in the regulation of energy balance and feeding behavior. Its expression in key brain regions involved in energy homeostasis suggests that activation of NPBWR1 contributes to the control of food intake through mechanisms that operate independently of the classical leptin and melanocortin pathways, highlighting the receptor’s versatile impact on both central and peripheral physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Juan Sandoval, Jesus Mendez-Gonzalez, Ernest Nadal, et al. 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