FGD4 encodes FRABIN, a guanine nucleotide exchange factor (GEF) that activates the small GTPase CDC42 by exchanging bound GDP for GTP 1. This activation regulates actin cytoskeleton reorganization and cell shape 2. In the peripheral nervous system, FGD4 plays a critical role in Schwann cell myelination; loss of FRABIN in Schwann cells leads to aberrant myelination characterized by myelin outfoldings, mediated through dysregulation of NRG1 type III/ERBB2/3 signaling and impaired endocytic trafficking 1. Mutations in FGD4 cause Charcot-Marie-Tooth disease type 4H (CMT4H), an autosomal recessive demyelinating peripheral neuropathy 13. Both homozygous and compound heterozygous FGD4 mutations present with peroneal myoatrophy, progressive foot deformities, and neurogenic damage affecting motor and sensory fibers 3. Niacin treatment reduces myelin pathology in CMT4H models by restoring NRG1 signaling balance, suggesting a therapeutic avenue 1. Beyond neurological disease, FGD4 expression is elevated in prostate cancer where it promotes aggressive phenotypes through CDC42/PAK signaling, cell migration, and enhanced mesenchymal characteristics 2. FGD4 genetic polymorphisms also associate with chemotherapy toxicity in cancer patients 45, though mechanistic details remain unclear.