Abstract
Mutations in the Alpha-actinin-4 gene (ACTN4) cause a rare form of familial focal segmental glomerulosclerosis in humans. Individuals with kidney disease-associated ACTN4 mutations tend to have mild to moderate proteinuria, with many developing decreased kidney function progressing to end stage kidney disease. All of the disease-causing ACTN4 mutations identified to date are located within the actin-binding domain of the encoded protein, increasing its binding affinity to F-actin and leading to abnormal actin rich cellular aggregates. The identification of ACTN4 mutations as a cause of human kidney disease demonstrates a key cellular pathway by which alterations in cytoskeletal behavior can mediate kidney disease. Here we review the studies relevant to ACTN4 and its role in mediating kidney disease.