Concurring with the notion that mitophagy plays a protective role in proximal tubular cells under pathogenic conditions, our study further illuminates the important therapeutic implication of MANF as a mitophagy/autophagy activator in ADTKD-UMOD, which can also directly promote autophagic clearance of mutant UMOD. This evidence concerns the gene MANF and autosomal dominant medullary cystic kidney disease with or without hyperuricemia.