PRKAA1 encodes the catalytic alpha-1 subunit of AMP-activated protein kinase (AMPK), a critical cellular energy sensor that regulates metabolism in response to ATP depletion 12. Upon energy stress, AMPK phosphorylates metabolic enzymes and transcription factors to inhibit ATP-consuming biosynthetic pathways (protein, lipid, carbohydrate synthesis) while activating energy-producing processes 12. PRKAA1 regulates lipid metabolism by phosphorylating acetyl-CoA carboxylase and hormone-sensitive lipase, thereby suppressing fatty acid and cholesterol synthesis 3. The kinase coordinates glucose homeostasis by phosphorylating CRTC2 and promoting GLUT4 translocation to enhance glucose uptake 4. PRKAA1 inhibits mTORC1 signaling through phosphorylation of RPTOR and TSC2, promoting autophagy and cell survival under nutrient limitation 5. Notably, AMPK-mediated phosphorylation of BECN1 promotes ferroptotic cell death by blocking system Xc- activity, with therapeutic implications for cancer treatment 6. PRKAA1 activation is crucial for resolving metabolic dysfunction: it alleviates non-alcoholic fatty liver disease through the miR-802/AMPK pathway 3, restores autophagy in diabetic nephropathy via CAMKK2-dependent activation 7, and coordinates glycolytic reprogramming with antimicrobial responses during bacterial infection 8. A PRKAA1 genetic polymorphism (rs13361707) shows no independent association with gastric cancer risk 9.