In this study, for the first time, the matching pattern of Ezrin/Periaxin expression regulated myoblast differentiation/fusion, myotube length and size, and myofiber specialization, and the combination of injected adenovirus vector carrying Ezrin (Ad-Ezrin) into the gastrocnemius muscle (GA) with injection of Ad-shPeriaxin into the GA or incubation of Ad-Periaxin within the injured peroneal nerve increased the number of MyHC-I/II myofibers, resulting in the recovery of GA atrophy in a peroneal nerve injury model, providing a novel therapeutic strategy for muscle atrophy, especially in CMT4F. Here, EZR is linked to muscle atrophy.