The Nogo receptor is a leucine-rich repeat (LRR) containing protein with a glycosylphosphatidylinositol (GPI) anchored C-terminus. The receptor was identified on the basis of its ability to bind with high affinity to Nogo-A a member of the reticulon family expressed in the cell membrane of oligodendrocytes.¹

Nogo-A attracted attention when it was demonstrated that it is a myelin protein capable of inhibiting axonal growth following nerve injury.^2,3  Other myelin proteins also identified as axonal growth inhibitors are the myelin-associated glycoprotein (MAG) a sialic-dependent immunoglobulin-like family member lectin (SIGLEC) and the oligodendrocyte myelin glycoprotein (OmgP) which is a GPI-anchored membrane protein.  Remarkably, despite their structural diversity, all three axonal growth inhibitors bind to the Nogo receptor with high affinity.^4,5

Since the Nogo receptor is a GPI-anchored protein it was expected that it would require another protein component to transduce the Nogo-A binding information into the responding neurons interior. Indeed, it was shown that the neurotrophin receptor p75 (p75^NTR) interacts with Nogo receptor and a third protein termed LINGO-1 to mediate axonal growth inhibition signaling.^6,7