NECAB2 (N-terminal EF-hand calcium binding protein 2) is a neuronal-specific calcium-binding protein that functions as a signaling scaffold protein modulating G-protein coupled receptor (GPCR) activity 12. The protein is abundantly expressed in telencephalon, habenula, and cerebellum, with peri-synaptic distribution in glutamatergic and GABAergic neurons 1. NECAB2 specifically interacts with metabotropic glutamate receptor 5 (mGluR5) and adenosine A2A receptor in a calcium-regulated manner, where increasing calcium concentrations reduce protein-protein interactions 23. These interactions modulate receptor function by regulating cell surface expression, ligand-induced internalization, and downstream MAPK/ERK1/2 signaling pathways 23. Disease relevance includes associations with autism spectrum disorders, as de novo NECAB2 deletions are linked to idiopathic autism, with knockout zebrafish models showing decreased locomotor activity and impaired social interactions 1. NECAB2 is also implicated in neuropathic pain through interactions with TRPV1 4, and differential expression has been observed in suicide victims and neurodegenerative diseases including Parkinson's disease 56. The protein serves as a potential biomarker in hepatocellular carcinoma prognosis 7.