GGH (γ-glutamyl hydrolase) is involved in the removal of γ-linked polyglutamates, thereby hydrolysing (anti)folylpoly-γ-glutamates. The enzyme controls the intracellular folate pools and folate metabolism. During the treatment of acute lymphoblastic leukemia (ALL), mutation in the GGH gene is linked with efficacy and side effects of methotrexate (MTX). It is responsible for changing a long-chain methotrexate polyglutamates (MTX-PGs) into a short-chain MTX-PGs and finally to MTX. Mutation in this gene at -401C>T enhances the response of cisplatin-based chemoradiotherapy in cervical carcinoma. The levels of GGH are higher in invasive breast cancer tumors and are associated with the development and progression of the cancer.
