HK2 shuttles from the cytoplasm to the mitochondria in response to environmental and metabolic stress, so HK2 ubiquitination by HectH9 E3 ligase at lysine K63 residue regulates its mitochondrial localization, regulating cancer stem-cell (CSC) expansion, promoting glycolysis, inhibiting apoptosis, and enhancing CSC-associated drug resistance [175]. Here, HK2 is linked to cancer.