Piezo1 dictates K? homeostasis through coordinated regulation of the ubiquitin ligase Kelch-like 3 in RBCs and the kidney

The maintenance of potassium (K+) balance is a fundamental biological process involving multiple organs. However, mechanisms by which inter-organ communication regulates K+ homeostasis remain largely unexplored. By combining human genetics and mouse model generation using CRIPSR/Cas9, we demonstrate that the ubiquitin ligase Kelch-like 3 (KLHL3) orchestrates K? transport across K?-storing erythrocytes and K?-excreting kidneys by interacting with the mechanosensitive Ca2+ channel Piezo1. Overall design: We compared RNA profiles obtained from the spleen between wild-type and KLHL3 knock-in mice.