# Unraveling GDAP1: Bridging Mitochondrial Biology and Peripheral Neuropathy

## TL;DR

This review explores how GDAP1, a mitochondrial protein, influences nerve health and disease, offering insights into potential treatments for inherited neuropathies.

## Contribution

The paper provides a comprehensive overview of GDAP1's role in mitochondrial and neuronal function, linking it to peripheral neuropathy.

## Key findings

- GDAP1 regulates mitochondrial fission, transport, and redox homeostasis in peripheral neurons.
- Genetic variants in GDAP1 are causally linked to Charcot–Marie–Tooth disease.
- OMM dysfunction due to GDAP1 impairment may be a key target for treating inherited neuropathies.

## Abstract

The mitochondrial outer membrane (OMM) plays a crucial role in maintaining cellular homeostasis by regulating mitochondrial dynamics, organelle interactions, and stress responses. In peripheral neurons—cells with high metabolic demands and long axons—the OMM acts as a vital platform for coordinating bioenergetics, calcium signaling, and redox balance. Ganglioside-induced differentiation-associated protein 1 (GDAP1), an OMM-anchored protein, has emerged as a key regulator of mitochondrial fission and transport, redox homeostasis, and mitochondrial membrane contact sites (MCSs). Genetic variants in GDAP1 cause Charcot–Marie–Tooth disease (CMT), emphasizing its essential role in peripheral nerve function. This review highlights the multifaceted functions of GDAP1 in neuronal physiology and as a model protein that integrates organelle communication and mitochondrial biology. We further discuss how GDAP1 dysfunction leads to structural and functional impairments in peripheral neurons, proposing the OMM and its microenvironment as critical targets for therapeutic intervention in inherited neuropathies.