{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nASPP2, encoded by TP53BP2, is a multifunctional protein that plays a central role in regulating epithelial plasticity, cell polarity, and apoptosis during development and tumor suppression. It promotes the mesenchymal–epithelial transition (MET) and counteracts epithelial–mesenchymal transition (EMT) by interacting with components of cell junctions—such as PAR‐3—to stabilize E‐cadherin/β‐catenin complexes, thereby maintaining tight junction integrity and proper tissue architecture. These activities are critical in organs such as the kidney and brain, where ASPP2 ensures correct neural progenitor organization, while its loss correlates with diminished junctional integrity and increased invasion in tumor models. Furthermore, under conditions including hypoxic stress, ASPP2 levels are regulated by ubiquitin ligases such as Siah2 to modulate cell polarity and adhesion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nASPP2 also functions as a potent tumor suppressor by enhancing p53‐mediated apoptosis and by modulating several key signaling pathways. It augments the apoptotic response through its interaction with p53 and related family members—rendering cells more sensitive to DNA damage—and its haploinsufficiency is associated with spontaneous tumor development in multiple in vivo models. In addition, ASPP2 influences oncogenic signaling cascades such as those mediated by Ras, where its interactions modulate nanoclustering and can shift Ras signaling toward senescence rather than transformation. It further intersects with insulin receptor substrate pathways and engages with mediators like MEK/ERK and NF‑κB, thus integrating signals that regulate cell proliferation, senescence, and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in development and tumor suppression, ASPP2 modulates cellular responses to injury and metabolic stress. In models of acute kidney injury and liver damage—including chronic liver disease and viral hepatitis—ASPP2 deficiency has been shown to attenuate apoptosis and enhance autophagic responses, thereby mitigating tissue injury and inflammation. Moreover, dysregulation of ASPP2—through chromosomal microdeletions or altered signaling—has been implicated in neurodevelopmental disorders and in altering the metabolic state of the liver, where it affects lipid homeostasis and may influence gut microbiota composition. These multifaceted functions underscore ASPP2 as a critical molecular switch that integrates signals from cell polarity, apoptotic, and survival pathways across diverse pathophysiological contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yihua Wang, Fangfang Bu, Christophe Royer, et al. 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