MPZ (myelin protein zero) is an adhesion molecule essential for normal peripheral nervous system myelination, functioning as a member of the immunoglobulin superfamily with single extracellular, transmembrane, and cytoplasmic domains 1. The protein mediates adhesion between adjacent myelin wraps through homotypic interactions of its extracellular domains and is necessary for myelin compaction; mice lacking MPZ develop severe dysmyelinating neuropathies with dramatically disrupted compaction 1. MPZ mutations cause inherited demyelinating neuropathies collectively termed Charcot-Marie-Tooth disease (CMT), with account for approximately 5.3% of genetically identified CMT cases 2. Specific mutation types correlate with phenotypic severity: mutations adding charged amino acids, altering cysteines, or truncating the cytoplasmic domain cause severe early-onset neuropathy through significant disruption of MPZ tertiary structure and adhesion function, while mutations more subtly altering structure cause late-onset disease 1. MPZ mutations cause diverse CMT presentations including CMT1B (demyelinating type 1B), Dejerine-Sottas syndrome (severe infantile-onset), and axonal CMT2 forms 3. Emerging therapeutic approaches for MPZ-associated disease include Unfolded Protein Response intervention to rescue misfolded MPZ proteins 4.