LRRC4 (leucine-rich repeat containing 4), also known as netrin-G ligand-2, is a multifunctional synaptic adhesion protein with significant roles in neural development and disease suppression. Primarily, LRRC4 regulates excitatory synapse formation and lamina-specific dendritic segmentation through recruitment of pre- and postsynaptic proteins 1. It functions as a PAR polarity complex member promoting axon differentiation and synaptic plasticity, facilitating memory formation and hippocampal information processing 2. Mechanistically, LRRC4 acts through multiple signaling pathways. In gliomas, it suppresses proliferation by downregulating STMN1 expression and inhibiting ERK/AKT signaling via the SDF-1α/CXCR4 axis, reducing angiogenesis and invasion 34. Loss of LRRC4 function creates regulatory loops involving miRNA, transcription factors, and DNA methylation modifications 12. Beyond oncology, LRRC4 demonstrates broader clinical relevance. LRRC4 deficiency drives premature ovarian insufficiency by disrupting mitochondrial metabolic homeostasis in granulosa cells 5. LRRC4 provides neuroprotection in experimental autoimmune encephalomyelitis by suppressing NF-κB signaling and Th1 immune responses 6. Mutations in LRRC4 associate with rosacea through neurogenic inflammation via excessive vasoactive peptide release 7. Notably, LRRC4 expression is significantly reduced in nasopharyngeal carcinoma compared to benign tissues 8, supporting its broad tumor-suppressive function across multiple tissue types.