In prostate cancer (PCa) models, the ubiquitination of Lys-63 residues by HECTH9 E3 ligase has been shown to further promote the localization of HK2 on the mitochondrial surface, resulting in the binding of HK2 to VDAC on the outer mitochondrial membrane and subsequent expansion, metabolic recombination, and chemical resistance of cancer stem cells [39]. The gene discussed is HUWE1; the disease is cancer.