HK1 and cancer: Mitochondrial-bound HK, considered the rate-limiting enzyme of glycolysis, is overexpressed in cancer (1, 23, 118) and, as discussed in Section “VDAC Interaction with HK and Other Metabolism-Related Proteins,” is associated with VDAC1, an interaction that offers several advantages to cancer cells (1, 11), as outlined below (see VDAC Interaction with HK and Other Metabolism-Related Proteins).