Glutamate carboxypeptidase 2 (PSMA)

Glutamate carboxypeptidase 2 (GCPII), widely known as prostate-specific membrane antigen (PSMA), is a type II transmembrane zinc metalloenzyme that functions as both a folate hydrolase and a neuropeptidase [11, 17]. It is primarily expressed in the prostate, central nervous system, and small intestine, where it catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) into N-acetylaspartate and glutamate [1, 18]. In oncology, PSMA is a critical therapeutic target due to its significant overexpression (100- to 1000-fold) on the surface of prostate cancer cells, particularly in metastatic and castration-resistant stages [1, 4]. This high expression allows for the precise delivery of radiopharmaceuticals, such as Lutetium-177 vipivotide tetraxetan, which bind to the extracellular domain and are internalized to deliver localized radiation [15, 16]. Beyond prostate cancer, GCPII is investigated as a target for neurological disorders like schizophrenia and neuropathic pain due to its role in regulating glutamatergic signaling [17, 18]. Therapeutic challenges include off-target uptake in salivary glands and kidneys, leading to side effects such as xerostomia and potential renal toxicity [8, 15].

Other names

Prostate-specific membrane antigenFOLH1Folate hydrolase 1N-acetyl-alpha-linked acidic dipeptidase INAALADase IFolylpoly-gamma-glutamate carboxypeptidaseFGCPMembrane glutamate carboxypeptidasemGCPCell growth-inhibiting gene 27 protein

Targeted radioligand therapy delivering beta or alpha radiation to cells upon internalization; diagnostic imaging via high-affinity binding of radiotracers for PET/SPECT visualization; enzymatic inhibition to modulate glutamatergic neurotransmission.