Ganglioside-induced differentiation-associated protein 1 (GDAP1) (GDAP1)

Ganglioside-induced differentiation-associated protein 1 (GDAP1) is an integral protein of the outer mitochondrial membrane primarily expressed in neural tissues [UniProt: Q8TB36]. It plays a critical role in regulating mitochondrial morphology by promoting mitochondrial fission and maintaining the connectivity of the mitochondrial network [PubMed: 26073153]. Structurally, GDAP1 contains glutathione S-transferase (GST)-like domains, which are implicated in cellular redox homeostasis and protection against oxidative stress [NCBI Gene: 84332]. Mutations in the GDAP1 gene are a major cause of Charcot-Marie-Tooth (CMT) disease, leading to various clinical phenotypes including CMT4A, CMT2K, and CMT1H [OMIM: 606598]. These mutations result in mitochondrial dysfunction, impaired calcium signaling, and increased susceptibility to apoptosis, ultimately causing the degeneration of peripheral nerves [PubMed: 30103345]. While there are currently no FDA-approved drugs specifically targeting GDAP1, it is a significant focus for gene therapy and research into small molecules that can restore mitochondrial dynamics [PubMed: 33511568].

Other names

GDAP1Ganglioside-induced differentiation-associated protein 1

Therapeutic strategies focus on gene replacement therapy to restore functional protein levels, modulation of mitochondrial fission and fusion pathways, and reduction of oxidative stress through GST-like domain activity.