Neurexins (NRXNs) are a family of transmembrane, synaptic adhesion molecules. NRXNS were identified as receptors for α-latrotoxin, a presynaptic toxin that triggers massive neurotransmitter release¹. Neurexins are largely presynaptic proteins that form a trans-synaptic cell-adhesion complex with postsynaptic neuroligins². They are encoded by three genes (NRXN1, NRXN2 and NRXN3), each using an upstream promoter to produce the longer α-isoform (α-NRXNs) and a downstream promoter to generate a shorter β-isoform (β- NRXNs).

The α- and β-isoforms of each neurexin are single-pass transmembrane proteins maintaining identical transmembrane and intracellular domains but having distinct extracellular domains. NRXNs in neurons localize to the presynaptic membrane and bind trans-synaptically to postsynaptic adhesion molecules and receptors³. Neurexins are expressed in all neurons, and are subject to extensive alternative splicing, generating >1,000 splice variants, some of which exhibit highly regulated developmental and spatial expression patterns⁴. 

The extracellular domain of neurexin 1α (NRXN1α) is composed of three neurexin repeats (I, II, and III), which each contains the modules LNS-EGF-LNS. NRXN1α binds endogenous ligands including neuroligins, LRRTM family members, neurexophilin, α-dystroglycan, and GABA(A) receptors.

NRXN1α gene mutations have been identified in neuropsychiatric diseases including Schizophrenia and Autism Spectrum Disorder⁵.