NPTXR (neuronal pentraxin receptor) is a transmembrane protein primarily involved in synaptic plasticity and neuronal circuit maturation. In the brain, NPTXR coordinates AMPA receptor clustering at excitatory synapses, particularly in parvalbumin-expressing interneurons, where it works with NPTX2 to promote GluA4-containing AMPAR expression and maintain proper circuit inhibition/excitation balance 1. NPTXR knockout mice display delayed circuit maturation, reduced feedforward inhibition, and increased seizure susceptibility, highlighting its role in network stability 1. Beyond neurobiology, NPTXR has emerged as a disease-associated protein. Cerebrospinal fluid NPTXR levels are reduced in Alzheimer's disease patients and decline progressively, correlating with disease progression independent of amyloid and tau pathology 2. NPTXR also represents a novel genetic risk factor for intracranial aneurysms 3 and ocular diseases including glaucoma 4. Notably, NPTXR is aberrantly expressed in gastric and esophageal cancers, where it promotes metastatic behavior through PI3K-AKT-mTOR and FAK-JNK signaling; anti-NPTXR monoclonal antibodies effectively inhibit cancer cell proliferation and metastasis 56. In SOD1-linked amyotrophic lateral sclerosis, NPTXR levels in cerebrospinal fluid respond to tofersen treatment and correlate with clinical response 7, suggesting potential as a biomarker for neurological disease progression.