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Glutathione S-transferases (GSTs) are a family of enzymes that catalyze the conjugation of the antioxidant glutathione (GSH) to a broad range of electrophilic compounds. This detoxification reaction increases the water solubility of xenobiotics and endogenous electrophiles, facilitating their elimination from the body. GSTs participate in the metabolism of drugs, environmental toxins, and products of lipid peroxidation, and they play roles in cellular redox regulation.

GSTs exist in multiple cellular compartments, including cytosol, mitochondria, and membranes. In humans, cytosolic GSTs are divided into several classes—Alpha (GSTA), Mu (GSTM), Pi (GSTP), Theta (GSTT), Zeta (GSTZ), and Omega (GSTO)—each encoded by distinct gene clusters. Most GSTs are homodimers of approximately 25–28 kDa subunits with two domains: an N-terminal thioredoxin-like domain and a C-terminal all-alpha-helical domain. The active site binds glutathione and the electrophilic substrate to form a GSH conjugate.

Genetic variation influences GST activity and substrate specificity. Common polymorphisms include null alleles GSTM1 and GSTT1, resulting in absent enzyme activity, and GSTP1 single-nucleotide changes that alter substrate preference. These differences can affect individual susceptibility to environmental carcinogens and responses to certain chemotherapies.

Clinically, GSTs contribute to chemical defense and may affect cancer risk, drug resistance, and toxicity profiles. Research continues into GST modulators as potential therapeutics and biomarkers for exposure history and treatment planning.