PMP2 Enhances Schwann Cell Metabolism and Promotes Myelination.

Myelinating Schwann cells depend on precise metabolic regulation to support axonal function and maintain peripheral nerve integrity. Peripheral Myelin Protein 2 (PMP2), a fatty acid-binding protein enriched in myelinating Schwann cells, has been implicated in lipid metabolism and mitochondrial energy production. Here, we examine the role of PMP2 in regulating Schwann cell bioenergetics and myelination. Using both immortalized and primary Schwann cells, we show that PMP2 overexpression enhances mitochondrial ATP production. We also reveal that PMP2 alters metabolic dependencies during high metabolic demand, reducing Schwann cell reliance on glutamine while promoting greater metabolic adaptability under substrate restriction. Finally, PMP2 overexpression significantly increases myelination in vitro, indicating that PMP2-driven metabolic modulation supports the energetic demands of myelination. These findings position PMP2 as a key regulator of Schwann cell metabolism and a potential therapeutic target for demyelinating neuropathies.