The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease

Berquez et al report a proof of concept for the repurposing of a class IA p110α PI3K inhibitor alpelisib for Lowe Syndrome/Dent disease 2, which are caused by loss-of-function mutations in the OCRL gene, which encodes the phosphatidylinositol [PI] 4,5-bisphosphate [PI(4,5)P₂] 5-phosphatase OCRL, and results in defective endocytosis and proximal tubule dysfunction.