This enzyme metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct.

Genetic polymorphisms that affect this enzyme's activity are correlated with variations in sensitivity and toxicity to such drugs.

[11] Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine.

Reuther et al. found that about 5% of all thiopurine therapies will fail due to toxicity.

[13] TPMT is now listed as a pharmacogenomic biomarker for adverse drug reactions to cisplatin by the FDA.