Alpha-actinin (α-
actinin) is a ubiquitous cytoskeletal
protein, which belongs to the superfamily of filamentous actin (
F-actin) crosslinking
proteins. It is present in multiple subcellular regions of both muscle and non-muscle cells, including cell-cell and cell-matrix contact sites, cellular protrusions and stress fiber dense regions and thus, it seems to bear multiple important roles in the cell by linking the cytoskeleton to many different transmembrane
proteins in a variety of junctions. Four
isoforms of human α-
actinin have already been identified namely, the "muscles" α-actinin-2 and α-actinin-3 and the "non-muscles" α-actinin-1 and α-actinin-4. The precise functions of α-
actinin isoforms as well as the precise role and significance of their binding to
F-actin particularly in-vivo, have been elusive. They are generally believed to represent key structural components of large-scale
F-actin cohesion in cells required for cell shape and motility. α-Actinin-2 has been implicated in
myopathies such as nemalin body
myopathy, hypertrophic and
dilated cardiomyopathy and it may have at least an indirect pathogenetic role in diseases of the central nervous system (CNS) like
schizophrenia,
epilepsy, ischemic brain damage, CNS lupus and
neurodegenerative disorders. The role of "non-muscle" α-actinins in the kidney seems to be crucial as an essential component of the glomerular filtration barrier. Therefore, they have been implicated in the pathogenesis of familial
focal segmental glomerulosclerosis,
nephrotic syndrome,
IgA nephropathy,
focal segmental glomerulosclerosis and
minimal change disease. α-
Actinin is also expressed on the membrane and cytosol of parenchymal and ductal cells of the liver and it seems that it interacts with hepatitis C virus in an essential way for the replication of the virus. Finally α-
actinin, especially α-actinin-4, has been implicated in
cancer cell progression and
metastasis, as well as the migration of several cell types participating in the immune response. Based on these functions, the accumulating reported evidence of the importance of α-
actinin as a target
autoantigen in the pathogenesis of
autoimmune diseases, particularly
systemic lupus erythematosus and
autoimmune hepatitis, is also discussed along with the possible perspectives that are potentially emerging from the study of this peculiar molecule in health and disease.