Abstract: Mammalian central nervous system (CNS) neurons lose axon regenerative ability as they mature. This failure to regenerate shows a clear contrast to a remarkable potential of axon growth during embryonic development and after an injury in the peripheral nervous system (PNS) (Hilton and Bradke, 2017). The absence of regeneration in the mature CNS neurons is caused by an inhibitory influence of the environment of the injured axons and the deficit of intrinsic factors that enable regeneration in the PNS (He and Jin, 2016). In the last two decades, gene manipulation strategies and compound screening have identified several neuron-intrinsic players involved in axon regeneration (Ribas and Costa, 2017). The central players are the PTEN/mTOR pathway, which contributes to protein synthesis, and transcription factors (such as SOCS3, KLF family, and SOX11) which control the cell differentiation/de-differentiation status. In addition, cytoskeletal dynamics at growth cones and material transport in axons are essential for axon regrowth; however, it is unclear how the components that regulate these functions are modulated in injured CNS neurons. In this study, we have discussed our recent discovery of an indispensable role of TC10 in CNS and PNS axon regeneration (Koinuma et al., 2020).