PRKAA2 encodes the α2 catalytic subunit of AMP-activated protein kinase (AMPK), a critical energy sensor that regulates cellular metabolism and homeostasis. PRKAA2 functions as a metabolic switch that activates energy-producing pathways and inhibits energy-consuming processes in response to cellular stress and nutrient availability 1. The protein plays essential roles in autophagy regulation, where it promotes autophagy-facilitated lipid clearance through the AMPK/SIRT1-TFEB pathway, particularly relevant in metabolic-associated fatty liver disease 1. In cardiovascular disease, PRKAA2 activity is modulated by post-translational modifications including phosphorylation and deubiquitination. Phosphorylation at T172 is critical for AMPK activation, while deubiquitination at specific residues can impair its function 23. Loss of PRKAA2 function contributes to diabetic cardiomyopathy through mitochondrial dysfunction, while its proper regulation protects against cardiac hypertrophy 3. Additionally, PRKAA2 phosphorylation enhances ACE2 stability in pulmonary endothelial cells, providing protection against pulmonary arterial hypertension 4. In cancer contexts, PRKAA2 can be targeted by microRNAs to promote chemoresistance 5. The gene also shows polymorphisms associated with growth traits in livestock 6.