Caspr1

Caspr1, also called CNTNAP1, is a neural cell adhesion molecule of the contactin-associated protein (Caspr) family. It is a single-pass transmembrane glycoprotein with a large extracellular domain that mediates interactions with its partner Contactin-1 (CNTN1) to form a transmembrane adhesion complex at the paranodal regions of myelinated axons. In the cytoplasmic tail, Caspr1 connects to intracellular scaffolding proteins such as 4.1B, linking the extracellular adhesion complex to the cytoskeleton.

In the CNS and PNS, Caspr1 localizes to the paranodes adjacent to the nodes of Ranvier, where it participates in organizing the axo-glial junctions that seal the seam between the axon and myelin sheath. This paranodal complex helps establish and maintain the barrier that restricts lateral diffusion of nodal membrane components and contributes to proper localization of ion channels, supporting saltatory conduction and nerve impulse speed.

Expression: Caspr1 is expressed in neurons and glial cells of the central and peripheral nervous systems, with enrichment at paranodal regions during myelination.

Clinical significance: Mutations in CNTNAP1, the gene encoding Caspr1, have been linked to severe congenital hypomyelinating neuropathies and brain malformations. Affected individuals may show hypotonia, developmental delay, and neuroimaging evidence of hypomyelination and structural brain anomalies. Less commonly, CNTNAP1 variants have been associated with epileptic or neurodevelopmental disorders.