Glutathione hydrolase 5 proenzyme

Glutathione hydrolase 5 (GGT5) is a proenzyme that cleaves the gamma-glutamyl bond of extracellular glutathione and glutathione conjugates, including leukotriene C4 and geranylgeranyl-glutathione (UniProt: P36269). This enzymatic activity releases cysteine necessary for both extracellular homeostasis and intracellular glutathione synthesis, while also regulating inflammatory mediators and lymphocyte positioning within lymphoid tissues.

GGT5 is expressed in extracellular and tissue-localized contexts where it participates in glutathione metabolism and immune regulation (UniProt: P36269). The enzyme modulates leukotriene signaling during inflammation and establishes geranylgeranyl-glutathione gradients that control lymphocyte trafficking and germinal center positioning.

GGT5 is upregulated in Alzheimer's Disease brain tissue relative to age-matched controls (Chaparral AD proteomics). In post-mortem AD brain analyzed by TMT-labeled proteomics across four subcellular fractions, GGT5 showed a mean log2 fold-change of 0.80, indicating increased expression in the disease state. This elevation may reflect altered glutathione metabolism or inflammatory responses characteristic of AD pathology.