PPARD (peroxisome proliferator-activated receptor delta) is a ligand-activated transcription factor that functions as a key mediator of energy metabolism in adipose tissues and other cell types 1. Once activated by ligands such as polyunsaturated fatty acids, PPARD binds to DNA promoter elements and regulates genes involved in fatty acid metabolism, particularly the peroxisomal beta-oxidation pathway and the acyl-CoA oxidase gene [UniProt]. PPARD plays a central role in metabolic reprogramming across multiple tissues: it drives fatty acid β-oxidation (FAO) in myeloid-derived suppressor cells in response to butyrate, with FAO activity dependent on PPARD-mediated transcription 2, and similarly promotes FAO-dependent self-renewal of leukemia stem cells through the FABP5/PPARD/CPT1A signaling axis 3. In glioblastoma, PPARD upregulation following HDAC inhibition shifts cancer metabolism toward oxidative phosphorylation and FAO, away from glycolysis 4. PPARD is overexpressed in lung adenocarcinoma and squamous cell carcinoma, where pathway analysis suggests it plays a mixed role with both protective and pro-tumorigenic functions 5. Additionally, PPARD genetic variants are associated with dynamic balance performance 6, indicating a role in muscle-related phenotypes. These findings establish PPARD as a critical metabolic regulator with disease implications in cancer, immune dysregulation, and athletic performance.