ACTN4 and focal segmental glomerulosclerosis: ,S6 Pathogenic ACTN4 variants cause podocyte injury and focal segmental glomerulosclerosis (FSGS1, OMIM: 603278S4).3, 4, 5, 6,S7,S8 Reported mutations cluster within the actin-binding domain, increasing actin affinity, and generating actin/ACTN4 aggregates4 (Supplementary Table S1 and Figure S1).