The alpha-actinins are a family of rod-like structural proteins related to spectrin and dystrophin. Humans have four alpha-actinin proteins, two of which (alpha-actinins-1 and -4) play important roles in the cytoskeleton, while the other two (alpha-actinins-2 and -3) form part of the contractile machinery in skeletal muscle. All alpha-actinins appear to function primarily in the cross-linking of actin filaments, allowing the formation of complex networks of filaments in the cytoskeleton and lending physical strength to the contractile apparatus of skeletal muscle.

Mutations in the gene encoding alpha-actinin-4 result in a condition known as familial focal segmental glomerulonephritis. Intriguingly, a mutation in the gene for the muscle isoform alpha-actinin-3 which completely abolishes the expression of protein appears to have no significant effect on human health - almost twenty percent of the normal population have this mutation in both copies of their alpha-actinin-3 gene with no obvious ill effect. This is the first known report of complete functional redundancy in a structural protein.