Elucidating the precise coupling of NgR1-dependent neuronal activity with the molecular restructuring of the node of Ranvier and paranodal myelin is a critical line of investigation in neuroscience that will drive the development of future regenerative therapeutic interventions that target the Nogo-A/NgR1 cell signaling mechanism during neurodegenerative diseases governed by the sequelae of inflammation. The gene discussed is RTN4R; the disease is neurodegenerative disease.