Neurofascin belongs to the L1 subgroup of the immunoglobulin superfamily of cell adhesion molecules and is an axon associated surface glycoprotein implicated in axonal growth and fasciculation.

Neurofascin is comprised of four structural elements: At the NH₂ terminus, neurofascin contains six Ig-like motifs of the C2 subcategory followed by four fibronectin type III (FNIII)-related repeats. Between the FNIII-like repeats and the plasma membrane spanning region, neurofascin contains a 75-amino acid residues rich in proline, alanine and threonine which might be the target of extensive O-linked glycosylation. A transmembrane segment is followed by a 113-amino acid residues-long cytoplasmic domain¹.

Neurofascin associates with sodium channel β₁ (Na_Vβ₁) units via interaction of its first Ig-like domain and second fibronectin type III–like domain with the extracellular Ig-like domain of β₁. Na_Vβ₁ subunits localize to nodes of Ranvier with neurofascin in sciatic nerve axons. Na_Vβ₁ and neurofascin are associated as early as postnatal day 5, during the period that nodes of Ranvier are in formation².

Unlike L1 and other subgroup members, neurofascin is subjected to extensive alternative splicing that is regulated during embryonic development of the brain. An oligodendroglial isoform of neurofascin, NF155, serves as a glial receptor for the paranodin/Caspr-contactin complex. The extracellular domain of NF155 binds to the complex at the cell surface³.