Neuroglycan C (NGC; also CSPG5 and CALEB) is a 120-150 kDa type I transmembrane glycoprotein and member of the neuregulin family of proteins. Depending on its expression profile, NGC may be a glycoprotein of 120 kDa, or a chondroitin sulfate (CS) proteoglycan of 150 kDa. Mouse NGC is synthesized as a 566 amino acid (aa) precursor that contains a 30 aa signal sequence, a 393 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 122 aa cytoplasmic region. The ECD contains one CS attachment domain (aa 32-273), with CS attachment at Ser117, one EGF-like domain (aa 371-413), three potential sites for N-linked glycosylation, and ten potential sites for O-linked glycosylation. Splicing variants produce four isoforms for human NGC. Isoform 1 is the standard form. Isoform 2 has a deletion of aa 487-513, while isoform 3 has an alternative start site at Met82 and the same deletion. Isoform 4 has a 56 aa substitution for aa 514-566. Phosphorylation likely occurs at Ser249, and proteolysis generates a 75 kDa soluble fragment. Over aa 31-420, mouse NGC shares 84% aa identity with human NGC. NGC is expressed in nervous tissue and is found on retinal ganglion cells, cerebellar Purkinje cells and hippocampal neurons. NGC may function as a growth and differentiation factor involved in neuritogenesis. One study shows that the recombinant ectodomain of NGC core protein enhances neurite outgrowth from rat neocortical neurons in culture via phosphatidylinositol 3-kinase and protein kinase C signaling pathways. Another study states that NGC is a novel component of midkine receptors, a heparin-binding growth factor that promotes cell attachment and process extension in oligodendroglial precursor-like cells. NGC also acts as a growth factor by directly binding ErbB3 tyrosine kinase and transactivating ErbB2.