One in ten people worldwide has chronic kidney disease (CKD)1. A subset of patients progresses to end-stage kidney disease (ESKD), which requires dialysis or transplantation and is a risk factor for cardiovascular disease and all-cause mortality1. CKD progression is linked to breakdown of the glomerular filtration barrier, the site of ultrafiltration in the kidney, which consists of endothelial cells, the glomerular basement membrane (GBM) and epithelial podocytes2,3. Podocytes have a unique architecture with foot processes that extend from their cell bodies, interdigitate and form slit diaphragms facilitating size and charge-selective filtration and preventing the loss of plasma proteins4,5. In health, podocyte shape is maintained by a complex, highly regulated actin cytoskeleton, which supports the foot processes6,7, and anchors the cell to the GBM8. During glomerular disease, the podocyte cytoskeleton becomes disorganised often leading to podocyte loss, impaired filtration and leakage of plasma proteins, such as albumin, into the urine7,9–11. Albuminuria is a hallmark of glomerular disease, irrespective of the underlying aetiology12. Therefore, therapies that protect the podocyte cytoskeleton represent a novel strategy to preserve the integrity of the glomerular filtration barrier, prevent albuminuria and improve glomerular disease progression. Thymosin β4 (TB4) sequesters monomeric G-actin in mammalian cells13,14 and maintains high concentrations of G-actin available for polymerisation into actin filaments (F-actin)15. We have previously shown that endogenous TB4 is expressed in podocytes and has a protective role. We found that lack of endogenous TB4
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