The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.
