Small RGK GTPases, Rad, Gem, Rem1, and Rem2, are potent inhibitors of high-voltage-activated (HVA) Ca²⁺ channels expressed in heterologous expression systems. However, the role of this regulation has never been clearly demonstrated in the nervous system. Using transcriptional analysis, we show that peripheral nerve injury specifically upregulates Gem in mice dorsal root ganglia. Following nerve injury, protein expression was increased in ganglia and peripheral nerve, mostly under its phosphorylated form. This was confirmed in situ and in vitro in dorsal root ganglia sensory neurons. Knockdown of endogenous Gem, using specific small-interfering RNA (siRNA), increased the HVA Ca²⁺ current only in the large-somatic-sized neurons. Combining pharmacological analysis of the HVA Ca²⁺ currents together with Gem siRNA-transfection of larger sensory neurons, we demonstrate that only the P/Q-type Ca²⁺ channels were enhanced. In vitro analysis of Gem affinity to various Ca_Vβx-Ca_V2.x complexes and immunocytochemical studies of Gem and Ca_Vβ expression in sensory neurons suggest that the specific inhibition of the P/Q channels relies on both the regionalized upregulation of Gem and the higher sensitivity of the endogenous Ca_V2.1-Ca_Vβ4 pair in a subset of sensory neurons including the proprioceptors. Finally, pharmacological inhibition of P/Q-type Ca²⁺ current reduces neurite branching of regenerating axotomized neurons. Taken together, the present results indicate that a Gem-dependent P/Q-type Ca²⁺ current inhibition may contribute to general homeostatic mechanisms following a peripheral nerve injury.