AbstractThe neurotrophin receptor p75 (p75NTR) is expressed by both neurons and glia. Nerve injury triggers up‐regulation of p75NTR in Schwann cells (SC) but not in central glia. In contrast to neuronal p75NTR, which mediates negative signals from myelin‐associated proteins resulting in neurite collapse, glial p75NTR may play a positive role in nerve regeneration by forming neurotrophin chemoattractant gradients or by competitively antagonizing the NOGO/NgR/LINGO‐1 signal through cell–cell contact or regulated intramembranous proteolysis (RIP) of p75NTR. This piece presents some recent evidence supporting this hypothesis. © 2007 Wiley‐Liss, Inc.