Point mutations in PLP1—the X chromosome gene encoding the most abundant myelin protein, myelin proteolipid protein (PLP)—occur at a low frequency in the population, and typically result in development of Pelizaeus-Merzbacher disease (PMD) or spastic paraplegia 2 (SPG2) in men, whereas female carriers are usually symptom-free [1]. Here, PLP1 is linked to paraplegia.