SH3TC2 (SH3 domain and tetratricopeptide repeats 2) is a protein essential for peripheral nerve myelination and the structural integrity of nodes of Ranvier in Schwann cells. The protein functions as a Rab effector involved in regulating endocytic recycling pathways, which are crucial for maintaining proper nerve function. Mutations in SH3TC2 cause Charcot-Marie-Tooth type 4C (CMT4C), an autosomal recessive demyelinating peripheral neuropathy 1. CMT4C typically manifests in childhood with distal motor weakness, sensory loss, foot deformities, and frequently presents with scoliosis and hearing loss 1. The disease shows progressive severity, with 48% of patients maintaining independent ambulation before age 50, but only 13% after age 50 1. Genotype-phenotype correlations indicate that patients with two truncating SH3TC2 variants exhibit more severe symptoms than those with one or no truncating variants 1. SH3TC2 is highly expressed in myelinating Schwann cells, and experimental gene therapy using AAV9 vectors to restore SH3TC2 expression has shown promise in mouse models, improving motor performance and normalizing node of Ranvier organization 2. Multiple pathogenic variants have been identified, with splice site mutations causing aberrant splicing patterns 3.