Citrate synthetase, also known as citrate (Si)-synthase, is an enzyme that plays a crucial role in the first step of the tricarboxylic acid (TCA) cycle, also known as the citric acid cycle or Krebs cycle. This enzyme catalyzes the condensation of acetyl-CoA with oxaloacetate (OAA) to form citrate, which is a key reaction in the metabolic pathway that generates energy through the oxidation of acetate groups derived from the breakdown of food molecules. The activity of citrate synthetase is important not only for the energy production through the TCA cycle but also because citrate provides a carbon source for the de novo synthesis of fatty acids and membrane lipids. Abnormal expression or mutation of citrate synthetase has been linked to various types of cancer, suggesting an oncogenic role for the enzyme. Additionally, citrate synthetase has been studied for its potential as a therapeutic target in conditions such as cancer and neurodegenerative diseases due to its involvement in mitochondrial function and energy metabolism.