Cytoskeleton Rearrangement in Podocytopathies: An Update Podocyte injury leads to disruption of the glomerular filtration barrier (GFB), causing podocytopathies, which are characterized by proteinuria and can progress to end-stage renal disease (ESRD). Podocytes, key cells in the GFB, maintain their structure through a coordinated cytoskeleton, including actin, microtubules, and intermediate filaments. Cytoskeleton rearrangement is central to podocytopathies, involving changes in slit diaphragm (SD) and focal adhesion proteins, such as nephrin, TRPC6, and Rho family regulators. This review discusses the molecular mechanisms of cytoskeleton rearrangement in podocytopathies and the effects of current drugs on regulating the podocyte cytoskeleton. Podocytopathies include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), and diabetic kidney disease (DKD). Podocyte injury disrupts the cytoskeleton, leading to foot process effacement (FPE), proteinuria, and chronic kidney disease (CKD). Actin cytoskeleton dysfunction is a major cause of FPE, with podocytes relying on actin for structure and function. Cytoskeleton rearrangement is influenced by various factors, including mechanical stress, genetic mutations, and signaling pathways. In FSGS, mutations in genes such as NPHS1, NPHS2, ACTN4, and TRPC6 are associated with podocyte injury and cytoskeleton disruption. Nephrin, a key SD protein, interacts with CD2AP and activates the Akt pathway, regulating actin cytoskeleton. RhoA and Rac1 activity also influence actin dynamics, with dysregulation leading to FPE and FSGS. Rab3A and Rabphillin-3A are involved in podocyte cytoskeleton rearrangement in FSGS. In MCD, nephrin and other SD proteins are altered, leading to cytoskeleton disruption. Autoantibodies against nephrin and ANXA2 are involved in MCD pathogenesis. In DKD, chronic hyperglycemia disrupts podocyte metabolism, leading to cytoskeleton rearrangement and apoptosis. Insulin and other signaling pathways regulate podocyte cytoskeleton, with CNIs like cyclosporine A and tacrolimus protecting podocytes by modulating Rho and Cdc42 signaling. In MN, autoantibodies against PLA2R cause immune complex deposition, leading to cytoskeleton disruption. In lupus nephritis (LN), miR-26a regulates podocyte cytoskeleton, and neutrophils contribute to podocyte injury. Therapeutic options include glucocorticoids, rituximab, and calcineurin inhibitors,Cytoskeleton Rearrangement in Podocytopathies: An Update Podocyte injury leads to disruption of the glomerular filtration barrier (GFB), causing podocytopathies, which are characterized by proteinuria and can progress to end-stage renal disease (ESRD). Podocytes, key cells in the GFB, maintain their structure through a coordinated cytoskeleton, including actin, microtubules, and intermediate filaments. Cytoskeleton rearrangement is central to podocytopathies, involving changes in slit diaphragm (SD) and focal adhesion proteins, such as nephrin, TRPC6, and Rho family regulators. This review discusses the molecular mechanisms of cytoskeleton rearrangement in podocytopathies and the effects of current drugs on regulating the podocyte cytoskeleton. Podocytopathies include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), and diabetic kidney disease (DKD). Podocyte injury disrupts the cytoskeleton, leading to foot process effacement (FPE), proteinuria, and chronic kidney disease (CKD). Actin cytoskeleton dysfunction is a major cause of FPE, with podocytes relying on actin for structure and function. Cytoskeleton rearrangement is influenced by various factors, including mechanical stress, genetic mutations, and signaling pathways. In FSGS, mutations in genes such as NPHS1, NPHS2, ACTN4, and TRPC6 are associated with podocyte injury and cytoskeleton disruption. Nephrin, a key SD protein, interacts with CD2AP and activates the Akt pathway, regulating actin cytoskeleton. RhoA and Rac1 activity also influence actin dynamics, with dysregulation leading to FPE and FSGS. Rab3A and Rabphillin-3A are involved in podocyte cytoskeleton rearrangement in FSGS. In MCD, nephrin and other SD proteins are altered, leading to cytoskeleton disruption. Autoantibodies against nephrin and ANXA2 are involved in MCD pathogenesis. In DKD, chronic hyperglycemia disrupts podocyte metabolism, leading to cytoskeleton rearrangement and apoptosis. Insulin and other signaling pathways regulate podocyte cytoskeleton, with CNIs like cyclosporine A and tacrolimus protecting podocytes by modulating Rho and Cdc42 signaling. In MN, autoantibodies against PLA2R cause immune complex deposition, leading to cytoskeleton disruption. In lupus nephritis (LN), miR-26a regulates podocyte cytoskeleton, and neutrophils contribute to podocyte injury. Therapeutic options include glucocorticoids, rituximab, and calcineurin inhibitors,