AMPK is a crucial cellular energy sensor that maintains energy homeostasis. It is activated by falling energy status, promoting ATP production by increasing catabolic pathways and conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole body level, influencing feeding behavior, circadian rhythms, and energy expenditure. Recent studies show that AMPK conserves ATP through non-metabolic processes like cell cycle regulation and neuronal membrane excitability. AMPK is a heterotrimeric complex composed of α, β, and γ subunits. Its activity is regulated by phosphorylation of the α subunit at Thr172, primarily by upstream kinases such as LKB1:STRAD:MO25 and CaMKKβ. AMP and ADP bind to the γ subunit, promoting phosphorylation and inhibiting dephosphorylation. AMPK is activated by metabolic stress, drugs, and xenobiotics, including metformin, resveratrol, and berberine. These activators increase cellular AMP and ADP levels, which in turn activate AMPK. AMPK also responds to oxidative stress and genotoxic treatments. It is activated by reactive oxygen species (ROS) and DNA-damaging agents, possibly through mechanisms involving ATM. AMPK plays a critical role in regulating cellular energy metabolism by activating catabolic pathways and inhibiting anabolic pathways. It regulates glucose uptake via the glucose transporter GLUT4, promoting glucose transport into cells by translocating GLUT4 to the plasma membrane. AMPK also regulates fatty acid uptake into cardiac myocytes and promotes mitochondrial biogenesis and mitophagy. It is involved in the regulation of anabolic pathways by inhibiting enzymes involved in lipid, carbohydrate, and protein synthesis. AMPK helps maintain energy homeostasis by conserving ATP and exerting a cytostatic, anti-tumor effect. AMPK influences whole-body energy metabolism, particularly through its actions in the hypothalamus. It regulates appetite by controlling the activity of neurons in the arcuate nucleus, which express neuropeptide Y and agouti-related protein (NPY/AgRP) or pro-opiomelanocortin (POMC). AMPK activation promotes feeding, while its inhibition reduces food intake. AMPK also plays a role in glucose sensing and the regulation of the sympathetic nervous system, influencing energy expenditure. AMPK is involved in circadian rhythms by regulating the expression of clock genes. It phosphorylates Cry1, affecting its interaction with Per2 and influencing the circadian period. AMPK functions beyond metabolism by regulating the cell cycle and membrane excitability. It promotes cell cycle arrest by phosphorylating cyclin-dependent kinase inhibitors and modulates neuronal membrane excitability by regulating potassium channels. AMPK is a key regulator of energy homeostasis, with roles in metabolism, cell cycle control, and neuronal function. Despite extensive research, many aspects of AMPK function remain to beAMPK is a crucial cellular energy sensor that maintains energy homeostasis. It is activated by falling energy status, promoting ATP production by increasing catabolic pathways and conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole body level, influencing feeding behavior, circadian rhythms, and energy expenditure. Recent studies show that AMPK conserves ATP through non-metabolic processes like cell cycle regulation and neuronal membrane excitability. AMPK is a heterotrimeric complex composed of α, β, and γ subunits. Its activity is regulated by phosphorylation of the α subunit at Thr172, primarily by upstream kinases such as LKB1:STRAD:MO25 and CaMKKβ. AMP and ADP bind to the γ subunit, promoting phosphorylation and inhibiting dephosphorylation. AMPK is activated by metabolic stress, drugs, and xenobiotics, including metformin, resveratrol, and berberine. These activators increase cellular AMP and ADP levels, which in turn activate AMPK. AMPK also responds to oxidative stress and genotoxic treatments. It is activated by reactive oxygen species (ROS) and DNA-damaging agents, possibly through mechanisms involving ATM. AMPK plays a critical role in regulating cellular energy metabolism by activating catabolic pathways and inhibiting anabolic pathways. It regulates glucose uptake via the glucose transporter GLUT4, promoting glucose transport into cells by translocating GLUT4 to the plasma membrane. AMPK also regulates fatty acid uptake into cardiac myocytes and promotes mitochondrial biogenesis and mitophagy. It is involved in the regulation of anabolic pathways by inhibiting enzymes involved in lipid, carbohydrate, and protein synthesis. AMPK helps maintain energy homeostasis by conserving ATP and exerting a cytostatic, anti-tumor effect. AMPK influences whole-body energy metabolism, particularly through its actions in the hypothalamus. It regulates appetite by controlling the activity of neurons in the arcuate nucleus, which express neuropeptide Y and agouti-related protein (NPY/AgRP) or pro-opiomelanocortin (POMC). AMPK activation promotes feeding, while its inhibition reduces food intake. AMPK also plays a role in glucose sensing and the regulation of the sympathetic nervous system, influencing energy expenditure. AMPK is involved in circadian rhythms by regulating the expression of clock genes. It phosphorylates Cry1, affecting its interaction with Per2 and influencing the circadian period. AMPK functions beyond metabolism by regulating the cell cycle and membrane excitability. It promotes cell cycle arrest by phosphorylating cyclin-dependent kinase inhibitors and modulates neuronal membrane excitability by regulating potassium channels. AMPK is a key regulator of energy homeostasis, with roles in metabolism, cell cycle control, and neuronal function. Despite extensive research, many aspects of AMPK function remain to be