Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (PubMed:23185017, PubMed:26985301, PubMed:29298880). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:29298880). Plays a key role in maintaining the integrity of the outer mitochondrial membrane by preventing the release of apoptogenic molecules from the intermembrane space and subsequent apoptosis (PubMed:18350175). ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+) ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+) ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+) Hexokinase activity is specifically inhibited by 2,6-disubstituted glucosamines. Carbohydrate metabolism; hexose metabolism. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4. Monomer (By similarity). Interacts with TIGAR; the interaction increases hexokinase activity in a hypoxia- and HIF1A-dependent manner (PubMed:23185017). The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (PubMed:29298880). The interaction with the mitochondrial outer membrane via the mitochondrial-binding peptide (MBP) region promotes higher stability of the protein (PubMed:29298880). Release from the mitochondrial outer membrane into the cytosol induces permeability transition pore (PTP) opening and apoptosis (PubMed:18350175). Predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle. The N- and C-terminal halves of the protein contain a hexokinase domain (PubMed:29298880). In contrast to hexokinase-1 and -3 (HK1 and HK3, respectively), both hexokinase domains display catalytic activity (PubMed:29298880). The region connecting the two hexokinase domains is required for the catalytic activity of the N-terminal hexokinase domain (PubMed:29298880). The N-terminal half regulates stability of the whole enzyme (PubMed:29298880). Although found in NIDDM patients, genetic variations of HK2 do not contribute to the disease (PubMed:7883122, PubMed:7883123). Belongs to the hexokinase family. Hexokinase is known to act as a monomer in normal conditions (By similarity). It however homodimerizes at elevated protein concentrations used for crystallizations (PubMed:26985301, PubMed:29298880). Hexokinase entry