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Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2\u2010related diseases in humans. On the one hand, studies on <jats:italic>Cntnap2<\/jats:italic> (coding for CASPR2) knockout mice revealed its role during development, especially, in setting\u2010up the inhibitory network. Consistent with this result, mutations in the <jats:italic>CNTNAP2<\/jats:italic> gene coding for CASPR2 in human have been identified in neurodevelopmental disorders such as autism, intellectual disability, and epilepsy. On the other hand, CASPR2 was shown to play a role beyond development, in the localization of voltage\u2010gated potassium channel (VGKC) complex that is composed of TAG\u20101, Kv1.1, and Kv1.2. This complex was found in several subcellular compartments essential for action potential propagation: the node of Ranvier, the axon initial segment, and the synapse. In line with a role of CASPR2 in the mature nervous system, neurological autoimmune diseases have been described in patients without neurodevelopmental disorders but with antibodies directed against CASPR2. These autoimmune diseases were of two types: central with memory disorders and temporal lobe seizures, or peripheral with muscular hyperactivity. Overall, we review the up\u2010to\u2010date knowledge on CASPR2 function and pinpoint confused or lacking information that will need further investigation.<\/jats:p>","DOI":"10.1111\/ejn.14081","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T14:38:04Z","timestamp":1532097484000},"page":"1906-1923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Contactin\u2010associated protein\u2010like 2, a protein of the neurexin family involved in several human diseases"],"prefix":"10.1111","volume":"48","author":[{"given":"Margaux","family":"Saint\u2010Martin","sequence":"first","affiliation":[{"name":"Institut NeuroMyoGene INSERM U1217\/CNRS UMR 5310 Universit\u00e9 de Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien","family":"Joubert","sequence":"additional","affiliation":[{"name":"Institut NeuroMyoGene 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