Folate hydrolase 1 (FOLH1)

Folate hydrolase 1 (FOLH1) is a type II transmembrane zinc metalloenzyme primarily known for its function as a carboxypeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate[1][3][7]. It is also recognized under several aliases, notably prostate-specific membrane antigen (PSMA), reflecting its high expression in prostate tissues and its major role in prostate cancer diagnosis and therapy[1][2][3]. FOLH1/PSMA is involved in both folate metabolism and neurotransmitter regulation via NAAG processing in neural tissues[3][7]. In oncology, it serves as a key biomarker and molecular target for imaging and targeted therapies, especially in metastatic prostate cancer[1]. FOLH1 encodes a glycosylated membrane protein that binds zinc and exists mainly in the extracellular membrane space, with a well-characterized substrate-binding pocket[1][2]. Expression of this molecule is not confined to the prostate: it is also present in various tissues such as the brain, small intestine, kidney, and salivary glands[2][4]. As PSMA, it is targeted by a variety of small molecule inhibitors and radioligands in both research and clinical practice, with potential safety concerns linked to its non-specific tissue expression[1][2][3].

Other names

Glutamate carboxypeptidase IIN-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I)Prostate-specific membrane antigen (PSMA)Folyl-poly-γ-glutamate carboxypeptidase (FGCP)NAAG peptidase

Enzyme inhibition (blockage of substrate hydrolysis, e.g., NAAG peptidase activity) Targeted radioligand therapy (delivery of cytotoxic/radiotherapeutic agent to FOLH1/PSMA-expressing cancer cells)