In this research, the PI3K inhibitor alpelisib suppressed aberrant actin polymerization by reducing levels of PI(4,5)P2 and PI(3)P, causing endocytosis defects in proximal tubules, increased megalin expression in the kidneys and reduced low-molecular–weight proteinuria and albuminuria in a humanized mouse model for Lowe syndrome/Dent disease-2. The gene discussed is LRP2; the disease is Dent disease.