-related disorders are rare genetic disorders due to somatic gain-of-function mutations in during embryonic development, a pathway involved in cell growth, proliferation, and metabolism. Accumulating evidence from patients with -related disorders indicates that peripheral nerves are frequently affected, leading to severe neurological symptoms. However, the exact underlying mechanism of these disorders remains unclear. To address this, we developed a mouse model with a gain-of-function mutation specifically in Schwann cells, which successfully mirrored the clinical features observed in patients. In this model, we observed that -mutated cells communicate with neighboring healthy cells, such as adipocytes and hair follicles, through a unique crosstalk mechanism that triggers their growth, proliferation, and anagen phase expansion. Additionally, we demonstrated that mutation in peripheral nerves leads to a metabolic shift through glycolytic activation. We investigated the effects of alpelisib, an approved pharmacological inhibitor of PIK3CA, in the model. Early administration of alpelisib significantly improved the signs and symptoms in the mice. However, when treatment was delayed, its efficacy was diminished due to the drug's inability to penetrate the myelin sheath effectively. In summary, our study offers a valuable mouse model for studying -related neuropathy, uncovers a unique communication between healthy and affected tissues, and highlights the potential benefits of early pharmacological intervention using alpelisib.