MAG (myelin-associated glycoprotein) is an adhesion molecule that mediates interactions between myelinating cells and axons through binding to neuronal sialic acid-containing gangliosides and glycoproteins RTN4R and RTN4RL2 1. While not required for initial myelination, MAG is essential for maintaining normal axon myelination and preventing degeneration of myelinated axons in adults [UniProt]. The protein protects motoneurons against apoptosis following injury, likely via RTN4R/RTN4RL2 interaction, and functions as a negative regulator of neurite outgrowth by inhibiting axon longitudinal growth and outgrowth through binding to these same receptors and gangliosides [UniProt]. MAG also shares a common signaling pathway with Nogo and OMgp proteins, converging on the Nogo66 receptor to inhibit axon growth 2. Clinically, MAG is a target antigen in anti-MAG neuropathy, an acquired chr19 demyelinating neuropathy characterized by distal sensorimotor neuropathy with IgM anti-MAG antibodies 3. The condition shows demyelination and axonal degeneration with IgG deposits at MAG localization sites 4. Therapy targets antibody reduction through rituximab (anti-CD20 B-cell monoclonal antibody), other anti-B cell agents, and novel antigen-specific immunotherapy 3. Genetic mutations in MAG are associated with spastic paraplegia 75, an autosomal recessive disorder [OMIM]. Anti-MAG serology combined with IgM-gammopathy detection optimizes diagnosis and predicts treatment response 5.