Neuroligin-1

Neuroligin-1 (NLGN1) is a cell surface protein that mediates cell-cell interactions through binding to neurexin family members (UniProt: Q8N2Q7). It plays a central role in synapse function and synaptic signal transmission by recruiting and clustering synaptic proteins, promotes initial synapse formation in vitro, and is required for maintaining wakefulness quality and normal cerebral cortex activity during sleep and wake states. The protein is essential for nervous system development.

NLGN1 is associated with autism spectrum disorder; mutations in NLGN1 cause Autism 20 (AUTS20, MIM 618830), an autosomal dominant developmental disorder characterized by social and communication impairments alongside restricted interests and often moderate intellectual disability (UniProt: Q8N2Q7).

In Alzheimer's disease, NLGN1 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.87; Chaparral AD proteomics). This down-regulation was observed in a TMT-labeled quantitative proteomics experiment examining four subcellular fractions, suggesting potential synaptic dysfunction in AD pathology.