Alpha-actinin-1 is a member of the spectrin superfamily of proteins and is an actin-binding protein with multiple roles in different cell types1. It is a component of the cytoskeleton and is involved in cross-linking actin filaments, which helps in maintaining cell shape, providing mechanical strength, and playing a role in cell motility and signal transduction. In nonmuscle cells, alpha-actinin-1 is found along microfilament bundles and adherens-type junctions, where it binds actin to the membrane. It is also present in muscle cells, where it helps anchor the myofibrillar actin filaments at the Z-discs and dense bodies. This protein is highly conserved and has been implicated in various biological processes, including cell migration, cell division, and the maintenance of cell structure. It is expressed ubiquitously and has been associated with several diseases. For instance, alpha-actinin-1 has been linked to myopathies, neurodegenerative disorders, and kidney diseases. It may also play a role in cancer cell progression and metastasis, as well as in the migration of immune cells. In terms of autoimmune diseases, alpha-actinin-1 has been identified as a potential target autoantigen, particularly in systemic lupus erythematosus (SLE) and autoimmune hepatitis. It is suggested that antibodies against alpha-actinin-1 may contribute to the pathogenesis of these diseases by cross-reacting with other proteins.