{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LRRC4 is a brain‐specific leucine‐rich repeat protein that plays dual, context‐dependent roles in the central nervous system. In normal neural tissue, LRRC4 (also known as netrin‑G ligand‐2) is critical for proper excitatory synapse development and dendritic spine maturation, thereby contributing to the specification and stability of neuronal connectivity and synaptic transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, LRRC4 appears to promote neurite extension and neuronal differentiation, suggesting its importance in both developmental processes and the maintenance of normal brain function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pathological contexts, LRRC4 functions as a potent tumor suppressor in gliomas. Its expression is frequently downregulated in high-grade gliomas, and experimental re‐expression of LRRC4 in glioma cells leads to several anticancer outcomes. Specifically, LRRC4 inhibits cell proliferation by causing a delay at the G0/G1 phase of the cell cycle and by modulating key signaling pathways including MEK/ERK, AKT, NF‑κB, STAT3, and JNK/c‑Jun."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " In addition, LRRC4 regulates autophagy via interactions with the DEPTOR/mTOR complex, thereby restoring sensitivity to chemotherapeutic agents such as temozolomide, and it attenuates glioma cell migration and invasion by altering the expression of key cytoskeletal regulators and cytokine signaling molecules."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that LRRC4 serves as a multifunctional protein with crucial roles in both healthy neuronal circuit formation and in suppressing glioma tumorigenesis. The loss of LRRC4 not only compromises synaptic organization and neuronal differentiation but also disrupts cell cycle regulation and pro-survival signaling pathways, underscoring its potential as a diagnostic marker and therapeutic target in brain tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seung Min Um, Seungmin Ha, Hyejin Lee, et al. 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