The neuroplastins Np55 and Np65 comprise a superfamily of neuronal and synapse enriched immunoglobulin molecules. They play an important role in a number of vital synaptic and neuronal activities including cell adhesion in the case of Np65. Np65 and Np55 are identical in structure except for the N-terminal Np65-specific Ig1 domain. They also play a key role in the localization of GABA(A) receptors in inhibitory synapses.

Neuroplastins have two Ig domains that project into the extracellular space and are followed by a single 21 amino-acid membrane spanning sequence and a 34 amino-acid intracellular domain. The intracellular domain is mostly comprised of charged and neutral residues but also of a few hydrophobic residues. The N-terminus includes a 28 amino-acid signal peptide. In addition, neuroplastins contain a glutamate residue in their transmembrane domain which is important for molecular interactions within the membrane region.

Although Np55 and Np65 are closely related in structure there are significant differences in terms of their expression. Np65 is tissue specific and is expressed mostly in forebrain neurons in the cortex, hippocampus and striatum. It has an anterior-posterior axis of expression. It is also expressed in lower amounts in the thalamus and hypothalamus. In contrast, Np55 is expressed throughout the brain in varying amounts.

Currently, neuroplastins are not directly implicated in human diseases however several possible links have been discovered. A single nucleotide polymorphism (SNP) in the human neuroplastin locus is associated with reduced cortical thickness and impaired intellectual ability in adolescents. Furthermore, other SNPs in neuroplastin has been found to be either a risk or protecting factor for schizophrenia in animal models¹.