CBLN2 (cerebellin 2 precursor) functions as a synaptic organizer that plays critical roles in neuronal circuit formation and pathological processes. The protein acts as a trans-synaptic bridging molecule, binding to postsynaptic GRID1/GRID2 receptors and presynaptic neurexins to organize excitatory synapses 1. CBLN2 shows functional redundancy with CBLN1 in the cerebellum, where both proteins can rescue synaptic deficits through common receptor binding properties 2. Beyond synaptic organization, CBLN2-expressing neurons form distinct circuit modules: in the spinal trigeminal nucleus, they coordinate repetitive self-grooming behaviors through brain-to-spinal pathways 3, while in the posterior hypothalamic nucleus, they regulate panic-like defensive states 4. CBLN2 has significant disease relevance, being upregulated in pulmonary hypertension where it promotes pathological endothelial-mesenchymal transition via NF-κB/HIF-1α/Twist1 signaling 5. In neuropathic pain, SOX11-mediated CBLN2 upregulation drives neuroinflammation through NF-κB activation 6. Additionally, CBLN2 marks tau-vulnerable neurons in Alzheimer's disease 7 and shows human-specific developmental regulation in prefrontal cortex spinogenesis 8, suggesting evolutionary adaptations in higher-order cognition.