Neuroplastin (NPTN) is a cell adhesion glycoprotein of the immunoglobulin superfamily that serves as a critical regulator of synaptic function and cognitive processes 1. As a primary function, NPTN mediates homophilic and heterophilic cell-cell adhesion and promotes long-term potentiation at hippocampal excitatory synapses through p38MAPK activation 2. Mechanistically, NPTN operates through multiple pathways: it acts as an obligatory chaperone for plasma membrane calcium ATPases (PMCA2), enabling their surface trafficking and facilitating rapid Ca2+ clearance at rates exceeding 5000 cycles/second—essential for terminating Ca2+ signals and maintaining cellular homeostasis 3. Additionally, NPTN regulates neurite outgrowth via FGFR1 signaling and controls synaptic plasticity through calcium signaling 1. Disease relevance is substantial: NPTN loss or pathway disruption associates with neuropsychiatric and neurodegenerative conditions including dementia, schizophrenia, and Alzheimer's disease 2. In Parkinson's disease, NPTN emerges as a potential synaptic-level biomarker 4, while in depression, the regulatory lncRNA NPTN-IT1-201 ameliorates depressive-like behaviors via the miR-142-5p/BDNF axis 5. Clinically, NPTN represents a novel cognition-related molecule with implications for treating nervous system diseases and potential as a therapeutic target, particularly for cognitive and mood disorders.