{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNINJ2 is a transmembrane adhesion molecule that has emerged from numerous genetic and clinical studies as a candidate contributing to diverse vascular and neurological disorders. Several studies have linked variants near or within the NINJ2 gene to ischemic stroke, coronary heart disease, dementia, multiple sclerosis, and even suicidal behavior. These association studies (e.g."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "support its involvement in disease susceptibility, suggesting that beyond being mere genetic markers, alterations in NINJ2 expression or function may underlie key pathological processes."}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies in vascular models have revealed that NINJ2 plays an important role in endothelial inflammation and activation. In human vascular endothelial cells, NINJ2 regulates a panel of inflammatory genes—including IL‑1β, TNF‑α, IL‑8, IL‑6, ICAM‑1, and E‑selectin—by modulating NF‑κB and c‑jun signaling through interactions with the TLR4 pathway. This pro‐inflammatory role may contribute to atherosclerosis and ischemic stroke risk. Moreover, in the context of multiple sclerosis, differential regulation of NINJ2 between monocytes and blood–brain barrier endothelial cells appears to influence monocyte transmigration into the central nervous system under inflammatory conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neuronal cells, NINJ2 functions as a pro‑survival factor and modulator of neuroregeneration. Its expression, which is abundant in neurons and glial cells, is subject to regulation by microRNAs such as miR‑764; downregulation of NINJ2 in this context leads to increased apoptosis, whereas its overexpression protects against oxidative stress. NINJ2 is also implicated in neurite outgrowth and nerve repair, as evidenced by its high expression in Schwann cells adjoining injured nerves and its suggested role in nerve regeneration. In contrast, in glioma cells, overexpression of NINJ2 promotes cell survival, proliferation, migration, and invasion through its interactions with receptor tyrosine kinases (EGFR, PDGFRβ, FGFR) and subsequent activation of Akt and Erk signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M Arfan Ikram, Sudha Seshadri, Joshua C Bis, et al. 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