Neurexins comprise a family of neuronal cell surface proteins, which include neurexin I (NRXN1), neurexin II (NRXN2), neurexin III (NRXN3) and Caspr (neurexin IV). Neurexins I-III are expressed as a and b isoforms. The a isoforms are made of three cassettes, which contain two LNS (Laminin A, Neurexins, Sex hormone-binding)-domains separated by EGF domains, followed by a transmembrane region and a 55 amino acid cytoplasmic C-terminal. The a isoforms bind to neurexophilins at the second LNS site and to the excitatory neurotoxin a-latrotoxin. The b isoforms have only one LNS-domain, bind to neuroligins, and play a role in the formation and remodeling of synapes. Caspr (for Contactin-Associated Protein 1, also designated Paranodin in mouse), contains an extracellular domain similar to the other three neurexins, and binds to the surface glycoprotein Contactin. Caspr and the closely related Caspr2, a mammalian homolog of Drosophila Neurexin IV (Nrx-IV), demarcate distinct subdomains in myelinated axons. Specifically, Caspr exists at the paranodal junctions, while Caspr2 colocalizes with Shaker-like K+ channels in the juxtaparanodal region. Caspr may play a role in the communication of glial cells and neurons during development.