ACPP

ACPP Full Name

acid phosphatase, prostate

ACPP Introduction

Acid phosphatase, prostate (ACPP), also historically referred to as prostatic acid phosphatase (PAP), ACP3, or 5′-nucleotidase, is a protein-coding gene that encodes a member of the histidine acid phosphatase family of enzymes. In humans, ACPP is primarily synthesized by the epithelial cells of the prostate gland under androgen regulation and secreted into seminal fluid, where it functions as a phosphomonoesterase to hydrolyze phosphate esters at acidic pH and generate free phosphate and alcohol products. The full-length mature human protein is about 354 amino acids long and typically forms a homodimer of approximately 95–100 kDa; alternative splice variants, including a transmembrane form (sometimes called TMPase), have also been described, with roles in endosomal-lysosomal trafficking and potential membrane localization. Beyond the prostate, ACPP is expressed in other tissues such as pain-sensing neurons in the spinal cord, where its enzymatic activity can dephosphorylate AMP to produce adenosine, a neuromodulator with analgesic effects.

Figure 1. The catalytic and secretory mechanisms of ACPP.

At the molecular level, ACPP functions as a non-specific tyrosine and acid phosphatase that dephosphorylates a broad range of substrates under acidic conditions (pH 4–6), including phosphorylated proteins and small molecule phosphate esters. This catalytic versatility reflects its classification in the histidine phosphatase family, with critical catalytic residues such as a histidine nucleophile and aspartate proton donor within the active site. In addition to phosphomonoester hydrolysis, ACPP exhibits 5′-nucleotidase activity, contributing to purine metabolism by converting AMP to adenosine in certain neural contexts and indicating a broader role in signaling and metabolic regulation beyond its classical enzymatic function in the prostate.

Clinically and historically, ACPP has been a biomarker in prostate cancer diagnosis and monitoring, especially before the widespread adoption of prostate-specific antigen (PSA) testing; elevations in serum PAP levels were associated with advanced or metastatic prostate carcinoma. Expression of secretory and transmembrane forms of ACPP is altered in neoplastic versus benign prostatic tissues, and research continues to explore ACPP's role as a tumor suppressor and regulator of cell growth, potentially through dephosphorylation of oncogenic signaling proteins such as ERBB2. Beyond oncology, genetic variation in ACPP has been linked to differences in enzyme levels in cerebrospinal fluid, suggesting emerging connections to brain biology and neurodegenerative or psychiatric conditions, although these associations remain under active investigation and are not yet fully characterized clinically.

Alternate Names for ACPP

ACPP; acid phosphatase, prostate; prostatic acid phosphatase; ACP 3; ACP3; TMPase; 5-nucleotidase; ecto-5-nucleotidase; thiamine monophosphatase; prostatic acid phosphotase; PAP; 5-NT; ACP-3;

• 1. Staley LA, et al.; Alzheimer's Disease Neuroimaging Initiative; Ridge PG, Goate AM, Kauwe JS. Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels.BMC Genomics. 2016, 17 Suppl 3(Suppl 3):439.