PPARA (peroxisome proliferator-activated receptor alpha) is a ligand-activated nuclear transcription factor that functions as a master regulator of lipid metabolism and energy homeostasis. As a key executor of fatty acid catabolism, PPARA heterodimerizes with RXRA to activate genes involved in peroxisomal beta-oxidation and hepatic autophagy 1. The receptor is activated by endogenous lipids including palmitoylethanolamide, which signals through PPAR-α-dependent pathways to exert anti-inflammatory effects 2. Mechanistically, PPARA regulates hepatic lipid homeostasis through multiple pathways: it coordinates with PCK1 during fasting to ameliorate non-alcoholic fatty liver disease (NASH) and fibrosis 3, modulates intestinal fatty acid uptake via FABP1 regulation 4, and controls hepatomegaly and liver regeneration through YAP-TEAD signaling activation 5. Additionally, PPARA transcriptionally activates SLC47A1 to protect against ferroptosis-induced cell death 6. Clinically, PPARA activation holds therapeutic potential for multiple diseases. PPARA agonists decrease amyloid-beta pathology and cognitive decline in Alzheimer disease models 1, while PPARA antagonism reduces obesity and NASH progression 4. Evolutionary studies demonstrate that PPARA haplotypes underwent positive selection in Tibetan populations for high-altitude adaptation 7, highlighting its fundamental role in metabolic homeostasis and hypoxia response.