H6PD, also known as hexose-6-phosphate dehydrogenase, is a microsomal enzyme that catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway [3]. This pathway is crucial for generating NADPH, which is involved in various biological processes such as antioxidant defense, steroid synthesis, and nucleotide biosynthesis.

In mice with a targeted mutation in H6PD, the oxo-reductase activity of 11β-hydroxysteroid dehydrogenase type 1 (11-HSD1) is drastically decreased, while its 11-dehydrogenase activity is increased. These mice share many phenotypic features with those having a mutation of 11-HSD1 itself, indicating H6PD's role in corticosteroid metabolism [2]. In human studies, a case-control study in Iranian Kurdish women found that variants of H6PD R453Q affect the risk of polycystic ovary syndrome (PCOS) [3]. Also, in gallbladder cancer, miR-551b-3p can target and inhibit H6PD expression, and overexpression of miR-551b-3p suppresses the epithelial-mesenchymal transition, migration, and invasion of gallbladder cancer cells [1].

In conclusion, H6PD is essential for the pentose phosphate pathway and thus for NADPH production. Its role in corticosteroid metabolism has been revealed through mouse models. Moreover, its gene polymorphisms are associated with PCOS, and its regulation by miRNAs is linked to gallbladder cancer progression. Understanding H6PD's functions provides insights into these disease mechanisms and may offer potential therapeutic targets.