NrCAM (Neuron-glia related cell adhesion molecule) is a cell adhesion molecule that belongs to the immunoglobulin-class (Ig) of the L1 family. NrCAM promotes axon growth and repulsion through trans homophilic binding of extracellular domains and intracellular coupling of the conserved cytoplasmic domains to the actin cytoskeleton. This interaction occurs through ankyrin B and ezrin-radixin-moesin adaptors. In addition, NrCAM is responsible for controlling dendritic spine densities, axonal guidance and targeting, and neurite outgrowth by acting as a co‐receptor molecule at the neuronal cell surface^1,2.

NrCAM is highly expressed in the cortex^1,3. Its structure contains a PDZ binding motif with the potential to bind PSD scaffold proteins PSD-95 and SAP102. The Ig domains of the protein mediate homophilic and heterophilic binding to multiple ligands^2,3.

Genetic polymorphisms in the NrCAM gene are linked to autism spectrum disorders, intellectual disability and addictive behavior. NrCAM knockout mice demonstrate autism spectrum disorder related behaviors including impaired sociability, cognitive inflexibility, hypersensitivity to sensory stimuli and altered visual cortical responses.