paraoxonase-2 (PON2)

Class

modulator (glabridin derivative)

Paraoxonase-2 (PON2) is a member of a small family of enzymes named for their original discovery as organophosphate-detoxifying proteins, though PON2 itself does not circulate in blood like its relative PON1. Instead, PON2 resides inside cells, particularly in mitochondria and the endoplasmic reticulum, where it helps limit oxidative stress by reducing the production of reactive oxygen species and by breaking down certain oxidized lipids and lactones through its enzymatic activity. This intracellular antioxidant function influences how cells manage energy production and respond to metabolic and oxidative challenges. Because oxidative stress and mitochondrial dysfunction contribute to conditions such as obesity, fatty liver disease, atherosclerosis, and neurodegenerative disorders, PON2 has drawn interest as a target whose activity might be adjusted to shift cellular energy handling or redox balance in a therapeutically useful direction. Modulators of PON2, including small molecules derived from plant-based compounds such as glabridin, are being explored for their ability to alter mitochondrial function in metabolically active tissues like fat and liver. The broader rationale is that changing PON2 activity could promote healthier energy expenditure and reduce lipid accumulation, making it relevant across a range of metabolic and inflammatory disease contexts.