Neurexin 1, also known as NRXN1a, is a neuronal type I transmembrane molecule that is encoded by one of three Neurexin genes (1, 2). Mature rat Neurexin 1 alpha is a 130 - 200 kDa N- and O-glycosylated protein with a 1424 amino acid (aa) extracellular domain (ECD) and a 55 aa cytoplasmic region. The ECD contains six LNS domains interspersed with three EGF-like domains and a juxtamembrane O-glycosylation region; the cytoplasmic domain contains a PDZ recognition motif (1, 2). The ECD of rat Neurexin 1 alpha shares 92% and 97% aa sequence identity with human and mouse Neurexin 1 alpha, respectively. It shares 68% aa sequence identity with rat Neurexin 2 alpha and 3 alpha. Transcription of the Neurexin 1 gene from an internal promoter gives rise to Neurexin 1 beta which lacks the first five LNS domains and all of the EGF-like domains (3). Neurexins are combinatorially spliced at five canonical sites, giving rise to over 1000 potential isoforms (3, 4). This recombinant protein corresponds to the ECD of SwissProt # Q63372, isoform 13, which has short deletions at splice sites 1 and 2. Neurexin 1 alpha is primarily expressed in the brain where it is localized to presynaptic terminals (3, 5). It binds black widow spider toxin alpha -latrotoxin, plus dystroglycan, neurexophilin 1 and 3, and the postsynaptic neuroligins (6 - 9). The interaction between Neurexins and neuroligins is complex and is restricted to particular combinations of splice forms of each binding partner (9). These interactions promote the differentiation and maintenance of postsynaptic GABA and NMDA, but not AMPA terminals (10, 11). At presynaptic terminals, as well as in pituitary melanotrophs, alpha Neurexins are required for coupling voltage-dependent calcium channel signaling to neurotransmitter or hormone release (12 - 14).