By using renal tubular Lonp1‐cKO or Lonp1‐cKI mice and proximal tubular epithelial cells, we demonstrated for the first time that LONP1 prevents the progression of renal fibrosis in two CKD models (UUO and 5/6Nx) by maintaining mitochondrial homeostasis. The gene discussed is LONP1; the disease is renal fibrosis.