α-Ketoglutarate dehydrogenase (α-KGDH) is a critical enzyme in Kerbs cycle (also known as the citric acid cycle or TCA cycle), a crucial metabolic pathway providing energy in aerobic respiration. This enzyme catalyzes the conversion of α-ketoglutarate into succinyl-CoA and CO2, a reaction that is both irreversible and highly exergonic. This step is significant not only for energy production, as it contributes to the generation of GTP (or ATP) and FADH2, but also for its role in metabolic integration, participating in amino acid metabolism, and regulating the TCA cycle. α-KGDH is a complex enzyme that requires several cofactors, including thiamine pyrophosphate (TPP), lipoic acid, NAD+, and FAD, to function. Due to its central role in metabolism, dysregulation or deficiency of α-KGDH is associated with various diseases, including neurodegenerative disorders such as Alzheimer’s, highlighting its importance in energy metabolism and disease pathogenesis.