SPTBN4 encodes spectrin beta, non-erythrocytic 4, a cytoskeletal protein essential for neuronal organization and function. As a non-erythrocytic β-spectrin, SPTBN4 assembles with α-spectrin subunits to form heterodimers that bind to cytoskeletal elements and the plasma membrane, enabling proper localization of ion channels, signal transduction, and cellular scaffolding 1. SPTBN4 plays specialized roles in axonal organization, including clustering of voltage-gated sodium channels at the node of Ranvier and maintenance of axonal domains critical for neuronal function 2. Pathogenic variants in SPTBN4 cause neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND), an autosomal recessive condition 3. Affected individuals present with severe muscular hypotonia, dysphagia, absent or delayed speech, gross motor and mental retardation, with variable features including nystagmus, epileptiform EEG discharges, and choreoathetosis 3. Muscle histology reveals both myopathic and neuropathic characteristics 3. However, clinical presentation varies; some patients exhibit primarily axonal neuropathy with hypotonia without intellectual disability or seizures 4. Animal models demonstrate that SPTBN4 deficiency causes severe myopathy, hind-limb paralysis, and tremors 5. These findings establish SPTBN4 as critical for maintaining neuronal cytoskeletal integrity and proper axonal function.