Although the pathogenesis of idiopathic focal segmental glomerulosclerosis (FSGS) may be heterogeneous, autosomal dominant and recessive forms of FSGS are recognized. Recently, mutations in alpha-actinin 4 (ACTN4) and podocin genes were reported in patients with such familial FSGS. However, whether mutations in ACTN4 and podocin genes are associated with sporadic FSGS has not been determined. In the present study, we clarified the relation between mutations in ACTN4 and podocin genes and sporadic FSGS. We analyzed these reported mutations in ACTN4 and podocin in five patients with chronic renal failure due to therapy-resistant FSGS by direct sequencing of polymerase chain reaction products of ACTN4 and podocin. We found a C to T transition at nucleotide 465 in the ACTN4 gene in all of patients, and a T to C transition at nucleotide 954 in exon eight of podocin gene in two of five patients, resulting in no amino acid substitutions. Other mutations were not found in ACTN4 and podocin genes. Our findings suggest that sporadic FSGS is a heterogeneous disease, since ACTN4 and podocin genes are not found in our patients with sporadic FSGS.