Hexokinase II (HK II) is an enzyme that plays a crucial role in glucose metabolism. It is a member of the hexokinase family, which consists of four members: HK I, HK II, HK III, and HK IV. HK II specifically phosphorylates a six-carbon sugar, known as hexose, to a hexose phosphate. This enzyme is particularly important as it is the first and rate-limiting step of glycolysis, where it converts glucose to glucose-6-phosphate (G-6P). HK II is predominantly found in insulin-sensitive tissues such as the heart, skeletal muscle, and adipose tissues . It is also upregulated in many types of tumors and is associated with the Warburg effect, which is the enhanced aerobic glycolysis observed in cancer cells. Beyond its fundamental role in glycolysis, HK II is increasingly recognized for its role in survival signaling pathways. It controls cellular growth, prevents the mitochondrial death pathway, and enhances autophagy. The expression of HK II is regulated by the Akt/mTOR pathway, and it is phosphorylated by Akt, which leads to increased mitochondrial binding and protection. HK II also binds and inhibits TORC1 to facilitate autophagy in response to glucose deprivation.