Summary: The myelin sheath surrounding human neurons acts as insulation and increases their rate of signal transmission. Peripheral myelin protein (PMP22) is a key transmembrane protein involved in neuron myelination, the dysfunction of which can lead to significant human neuropathies. This report provides direct evidence that disease-associated PMP22 mutants are unstable and can self-associate to form dimers to a greater extent than wild-type protein, providing mechanistic insight into diseases such as Charcot-Marie-Tooth and Dejerine–Sottas syndrome. To accomplish this, we link mass-selected gas-phase protein stability measurements to in vivo protein trafficking data, paving the way for the future use of such data in understanding such complex biochemical processes. Raw IM-MS data files have been deposited in Figshare ().