{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCIP2A, a multifunctional oncoprotein and endogenous inhibitor of protein phosphatase 2A (PP2A), plays a central role in neurodegenerative processes. Elevated CIP2A expression in Alzheimer’s disease (AD) brains leads to PP2A inhibition, which in turn drives tau and amyloid precursor protein (APP) hyperphosphorylation, enhanced Aβ production, synaptic degeneration, and ultimately cognitive deficits. In various experimental models, including cultured neurons, astrocytes, and transgenic mice, increased CIP2A levels have been linked to aberrant kinase activation, DNA damage responses, and Chk1-dependent signaling that exacerbate AD-like pathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neurodegeneration, CIP2A contributes to the maintenance and dysregulation of stem and progenitor cell populations as well as tumor progression. In the testis and neural regions, CIP2A supports self‐renewal and proliferation by stabilizing key regulators such as Myc and by influencing the expression of stem cell markers like PLZF. Moreover, CIP2A overexpression has been documented in a range of cancers—including breast and nasopharyngeal carcinoma—where it enhances malignant phenotypes through its interference with PP2A activity. Notably, CIP2A deficiency can also impair dendritic arborization leading to depression‐like behaviors, while restoration of its expression (for example via Oct4 regulation) can mitigate tissue injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCIP2A further exerts key functions in cell cycle progression, centrosome dynamics, and the DNA damage response. It interacts with factors such as NEK2 to facilitate centrosome separation and mitotic spindle organization, and it participates in the repair of DNA double-strand breaks by mediating the microtubule-dependent recruitment of repair complexes. In the immune system, CIP2A also modulates T-cell activation, thereby linking its regulatory functions to diverse cellular contexts from reproductive biology to immunological responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yang-Ping Shentu, Yuda Huo, Xiao-Long Feng, et al. 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