SPTBN5 (spectrin beta, non-erythrocytic 5) encodes a beta-spectrin subunit that functions as a cytoskeletal scaffolding protein. Spectrins are assembled from α and β subunits and serve as common components of cytoskeletons, binding to cytoskeletal elements and the plasma membrane to allow proper localization of essential membrane proteins, signal transduction, and cellular scaffolding 1. The protein localizes to various cellular compartments including the cytoplasm, plasma membrane, and photoreceptor structures, where it binds actin filaments and participates in cytoskeletal organization based on GO annotations. SPTBN5 variants have been associated with neurodevelopmental disorders, with four different families showing missense and nonsense mutations causing intellectual disability ranging from mild to severe, aggressive tendencies, craniofacial dysmorphisms, autistic behavior, and gastroesophageal reflux 2. Additionally, SPTBN5 appears to play roles in diverse pathological processes including colorectal cancer progression, where downregulation significantly decreases cell proliferation, migration, and clonogenicity 3, and has been implicated in progressive supranuclear palsy through genome-wide association studies examining tau neuropathology 4. The gene has also been identified in studies of sacral agenesis 5 and shows altered methylation patterns in World Trade Center-exposed populations 6, suggesting broader roles in human disease beyond neurodevelopment.