Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the human peripheral nerve, and, at a frequency of∼ 1/2,500, it represents one of the most common disease traits. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked trait. In addition, many sporadic cases occur and have often been shown to result from new dominant mutations. The disease has generally been divided into two major types, on the basis of results of electrophysiologic studies. The type 1 form, CMT1, is accompanied by decreased motor nerve conduction velocities and primarily affects the myelin. The type 2 form, CMT2, manifests normal or slightly reduced motor nerve conduction velocities with decreased amplitudes and primarily affects the axon. In the past several years, much has been learned about CMT1, with 112 linked loci delineated and 6 genes identified (reviewed in Lupski [1999] and Warner et al.[1999])(table 1). These genes encode proteins with various functions that are important for myelin formation, structure, and integrity. However, from a genetic standpoint, precious little has been learned about CMT2, because, to date, no single gene has been identified, despite reports of the existence of four different CMT2-linked loci (table 2). In this issue of the Journal, Mersiyanova et al.(2000) provide substantive evidence that they have identified the first CMT2 gene. The gene NF-L encodes neurofilament light protein, which is one of three major neurofilament protein constituents. Neurofilaments are important for the structure and function of axons and may be necessary for axonal transport, regeneration, and longevity. Although Mersiyanova et al. report a single mutation in a large Russian family segregating autosomal dominant CMT2, they nevertheless provide impor-