{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuroblastoma suppressor of tumorigenicity 1 (NBL1) is a secreted member of the DAN family that functions predominantly as an extracellular antagonist of bone morphogenetic protein (BMP) signaling. In developmental contexts, DAN proteins regulate key processes such as osteoblast differentiation and neuroblastoma cell cycle progression, with evidence showing that NBL1 (originally termed DAN) is transcriptionally upregulated in association with p73 activity and cellular stress stimuli, and can even interact with Slit proteins to inhibit monocyte chemotaxis, thereby influencing both tissue patterning and inflammatory cell migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its developmental roles, differential expression studies have revealed that NBL1 holds promise as a molecular marker in various cancers. Microarray analyses in pancreatic adenocarcinomas revealed a marked decrease in NBL1 expression relative to normal tissue, while studies in prostate cancer have similarly documented its downregulation compared to benign counterparts—findings that underscore its potential tumor‐suppressive role. In parallel, structural and mutagenesis studies comparing NBL1 to other DAN family members have identified key differences in the BMP-binding epitope that modulate its potency against specific BMP ligands. These structural insights, reinforced by related studies such as those examining Grem2 complexes, illustrate the functional diversity within the family in modulating BMP and possibly additional signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent clinical studies have further linked circulating NBL1 levels to renal pathophysiology. In patients with diabetic kidney disease, elevated serum NBL1 is strongly associated with increased glomerular lesions, podocyte injury, and a heightened risk of progression to end‐stage kidney disease. Similar associations have been observed in IgA nephropathy, suggesting that NBL1 not only serves as a promising biomarker for renal disease progression but may also actively contribute to kidney injury through its pro‐apoptotic effects on vulnerable cell populations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Shinbo, Toshinori Ozaki, Takahito Nakagawa, et al. 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