A study published in Science by Romagnani and colleagues has elucidated how estrogen signaling enhances the regenerative capacity of podocytes, critical kidney filtering cells, in females. This protective effect underlies the lower incidence of chronic kidney disease (CKD) observed in premenopausal women compared to men. The researchers used lineage tracing and single-cell RNA-sequencing in mice to demonstrate that estrogen receptor activation promotes podocyte renewal from renal progenitor cells, a mechanism amplified during pregnancy. Disruption of estrogen signaling resulted in diminished regeneration and development of preeclampsia-like phenotypes, linking hormone-driven kidney resilience to pregnancy outcomes and offering new therapeutic avenues for CKD and maternal health.