Contactin-associated protein-like 2 (CASPR2)

Contactin-associated protein-like 2 (CASPR2) is a member of the neurexin superfamily of transmembrane cell adhesion molecules in the vertebrate nervous system[1][2]. It is encoded by the CNTNAP2 gene on chromosome 7q35 and is expressed highly in the brain, localized at juxtaparanodes of myelinated axons[1]. CASPR2 forms complexes with other cell adhesion proteins such as contactin-2 (CNTN2), playing crucial roles in the clustering of voltage-gated potassium channels and regulating neuronal excitability[1][2][3]. CASPR2 also participates in neurite outgrowth, dendritic spine maturation, and maintenance of synaptic stability — functions that are vital for typical brain development and neural circuit formation[2][3]. Mutations or autoimmunity against CASPR2 are associated with various neurodevelopmental diseases, most notably a spectrum of disorders including epilepsy, autism, and Pitt–Hopkins-like syndrome[1][2][3]. CASPR2 undergoes complex proteolytic processing, and its dysfunction can lead to altered neuronal network activity and neurodevelopmental pathology[3].

Other names

CASPR2CNTNAP2 (gene symbol for encoding gene)Contactin-associated protein-like 2Neurexin IV homolog (historical context)

No approved small molecules or classic drugs are known to target CASPR2 directly. In autoimmune conditions, autoantibodies against CASPR2 result in pathogenic mechanisms such as neuronal hyperexcitability and seizures. Potential future mechanisms may involve modulation of protein-protein interactions or cleavage events important in neuronal development.