FAO and metabolism play a key role in tubule and kidney health. Proximal tubule epithelial cells have a high-energy need to transport filtered solutes. Kidney epithelial cells rely on FAO and mitochondrial oxidative phosphorylation to meet this high ATP demand. AKI and CKD are characterized by a defect in fatty acid oxidation and low ATP levels. This defect in metabolism contributes to epithelial dedifferentiation and renal failure. Abbreviations: CPT-1, carnitine palmitoyltransferase 1; OXPHOS, oxidative phosphorylation; PGC1α, proliferator-activated receptor γ co-activator 1α (i.e., PPARGC1A); RXR, retinoid X receptor.