SPTB (spectrin beta, erythrocytic) encodes a critical cytoskeletal protein that forms the structural foundation of the erythrocyte plasma membrane 1. As a major constituent of the cytoskeletal network, SPTB associates with band 4.1 and actin to create the cytoskeletal superstructure underlying the red blood cell membrane, enabling proper localization of essential membrane proteins and maintaining cellular architecture 1. SPTB functions as part of the spectrin complex, assembled from α and β subunits that bind to cytoskeletal elements and the plasma membrane to facilitate cellular scaffolding 1. Pathogenic variants in SPTB are primarily associated with erythroid cell disorders, most notably hereditary spherocytosis (HS), one of the most common hereditary hemolytic disorders 23. SPTB mutations cause HS through various mechanisms, including nonsense-mediated mRNA degradation leading to reduced gene expression and premature protein truncation 3. The resulting cytoskeletal dysfunction leads to increased generation of red blood cell microparticles and hemolysis 3. Clinically, SPTB sequencing is used for genetic diagnosis of HS and identification of causative variants enables appropriate genetic counseling and understanding of hereditary hemolytic disease pathogenesis 2. Additionally, SPTB expression serves as a blood-specific biomarker for forensic body fluid identification 4.