Significance Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating “dying back” neuropathy featuring a distal-to-proximal peripheral nerve degeneration seen in cancer patients undergoing chemotherapy. The pathogenenic mechanisms of CIPN are largely unknown. We report that in sensory neurons, the CIPN-inducing drug bortezomib caused axonopathy and disrupted mitochondria motility by increasing delta 2 tubulin (D2), the only irreversible tubulin posttranslational modification and a marker of hyper-stable microtubules. These data provide a new paradigm for the risk associated with enhanced tubulin longevity in peripheral neuropathy and suggest that targeting the enzymes regulating this tubulin modification may provide therapies that prevent the axonal injury observed in bortezomib-induced peripheral neuropathy.