{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Follistatin‐like 5 (FSTL5), a secreted glycoprotein and member of the follistatin family, has emerged as a multifaceted regulator in diverse biological contexts. In pediatric brain tumors, for example, immunohistochemical detection of FSTL5 in medulloblastoma identifies a subset of non‐WNT/non‐SHH tumors associated with high relapse rates and poor overall survival, thereby refining current molecular stratification schemes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In hepatocellular carcinoma, reduced expression of FSTL5 is commonly observed. Functional studies indicate that restoration or overexpression of FSTL5 inhibits cancer cell proliferation and survival while promoting apoptosis—effects that have been linked to modulation of the Wnt/β‐catenin signaling pathway and attenuation of epithelial–mesenchymal transition, ultimately suppressing tumor invasion and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the developing and adult nervous system, FSTL5 shows a highly restricted expression pattern—localized to regions such as the olfactory system, hippocampal CA3 area, and the granule cell layer of the cerebellum—suggesting a role in fine-tuning neuronal functions and possibly sensory processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n During embryonic limb and skeletal development, studies in murine models have demonstrated FSTL5 expression in condensing cartilage anlagen and in prehypertrophic chondrocytes. Although overexpression studies did not recapitulate overt congenital deformities like clubfoot, these findings implicate FSTL5 in tissue morphogenesis and growth plate regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In non‐mammalian species, such as the swimming crab "}, {"type": "i", "children": [{"type": "t", "text": "Portunus trituberculatus"}]}, {"type": "t", "text": ", FSTL5 is upregulated during limb regeneration—a result that hints at a conserved role in repair and regenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, genome‐wide association studies have linked FSTL5 gene variants to adverse drug reactions, such as thiopurine‐induced bone marrow suppression in inflammatory bowel disease patients, possibly through interactions affecting extracellular matrix components."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, differential expression analyses in gliomas have revealed that increased FSTL5 levels may serve to distinguish particular tumor subtypes, underscoring its emerging potential as a biomarker across multiple disease contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that FSTL5 functions as a critical modulator in cancer progression, neural development, tissue regeneration, and drug response, warranting further investigation into its underlying molecular mechanisms.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marc Remke, Thomas Hielscher, Andrey Korshunov, et al. 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