Gamma-glutamylcyclotransferase

Gamma-glutamylcyclotransferase (GGCT) is a 188-amino-acid enzyme that catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, playing a role in glutathione homeostasis (UniProt: O75223). The protein can also trigger cytochrome c release from mitochondria and induce apoptosis, implicating it in cellular stress responses.

GGCT is expressed in human tissues and localizes to subcellular compartments including mitochondria, consistent with its roles in metabolic and apoptotic signaling. No baseline disease associations are documented in UniProt.

In Alzheimer's disease, GGCT shows consistent downregulation in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.71 across 2 subcellular fractions; Chaparral AD proteomics). This reduction was detected via TMT-labeled proteomics across the P2, P3, S2, and S3 subcellular fractions. The decreased abundance of GGCT in AD brain may relate to impaired glutathione metabolism or altered mitochondrial regulation in neurodegeneration.