Given the hierarchical order starting from mitochondrial quality control failure for the eventual activation of multiple proinflammatory cytokines in our deletion mutation mice, we envision that treatment with the upstream p-AMPK enhancer MANF, which can restore homeostasis of dysfunctional mitochondria and inhibit STING activation, would be more effective in blocking activation of a myriad of inflammatory genes, including TNFα, in ADTKD-UMOD. Here, MANF is linked to autosomal dominant medullary cystic kidney disease with or without hyperuricemia.