Rab7 is a member of the Rab family, a subset of the Ras superfamily of small GTPases. Rab7 participates in trafficking late endosomes to the perinuclear lysosomal compartment and is required for autophagic degradation of long lived proteins. Mutations in Rab7 are causative of the progressive axonopathic disorder Charcot-Marie-Tooth type 2b, also known as ulcero-mutilating neuropathy. We are investigating the hypothesis that disease-causing mutations in Rab7 disrupt axonal homeostasis by impairing autophagic degradation of retrogradely transported, vesicle-associated substrates.