Spectrin is a large,cytoskeletal,and heterodimeric protein composed of modular structure of and subunits,it typically contains 106 contiguous amino acid sequence motifs called"spectrin repeats".Spectrin is crucial for maintaining the stability and structure of the cell membrane and the shape of a cell.Moreover,it contributes to diverse cell functions such as cell adhesion,cell spreading,and the cell cycle.Mutations of spectrin lead to various human diseases such as hereditary hemolytic anemia,type 5 spinocerebellar ataxia,cancer,as well as others.This review focuses on recent advances in determining the structure and function of spectrin as well as its role in disease.