{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTPPP3, also known as p20, is a microtubule‐associated protein that binds directly to microtubules and promotes their assembly—a function critical for proper cell division. In HeLa cells, RNAi‐mediated knockdown of endogenous TPPP3 was shown to suppress proliferation by inducing cell cycle arrest and causing mitotic abnormalities such as multipolar spindle formation and chromosome segregation errors, ultimately triggering apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in mitosis, TPPP3 has been implicated in developmental events. In the context of decidualization—a key process for embryo implantation—TPPP3 is highly expressed in both murine and human endometrial stromal cells. Silencing TPPP3 in these cells suppresses critical decidual markers (such as prolactin), disrupts the β‐catenin/NF‑κB/COX‑2 signaling cascade, and induces mitochondria‐dependent apoptosis. In non–small‐cell lung carcinoma, preliminary findings also suggest that TPPP3 exhibits oncogenic properties that may contribute to tumor metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancers, aberrant TPPP3 expression appears to modulate malignant behavior. In breast cancer models, elevated levels of TPPP3 promote cell proliferation, invasion, and migration—effects that have been linked to its influence on NF‑κB signaling and downstream effectors such as MMP‑2 and MMP‑9. Similarly, studies in oral squamous cell carcinoma have highlighted that higher TPPP3 expression is associated with enhanced tumorigenic properties. By contrast, in head and neck squamous carcinomas, reduced TPPP3 expression correlates with distinct immune infiltration patterns and poorer patient prognoses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTPPP3 also participates in vascular homeostasis. In studies using human umbilical vein endothelial cells exposed to palmitic acid overload, silencing TPPP3 was found to reduce apoptosis and reactive oxygen species production. Mechanistically, TPPP3 interacts with voltage‐dependent anion channel 1 (VDAC1), enhancing its protein stability and thereby modulating endothelial injury responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, TPPP3 holds relevance in neurodegenerative disorders. In the context of Parkinson’s disease, although TPPP3 shares microtubule‐stabilizing functions with its homolog TPPP1, it notably lacks binding affinity for α‑synuclein. This divergence suggests that TPPP3 may counteract the formation of the pathological TPPP1–α‑synuclein aggregates implicated in Parkinsonism. Moreover, emerging data in endometrial cancer point to an interplay between TPPP3 and regulatory microRNAs (for example, miR‑1827) in driving disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenbai Zhou, Xuanchun Wang, Lianxi Li, et al. 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