ENPP3 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 3) is a type II transmembrane protein belonging to the membrane-bound ectonucleotide pyrophosphatase/phosphodiesterase family (ENPPs/ENPPs). ENPP3 is involved in nucleotide signaling, particularly in regulating allergic responses in basal cells and mast cells, and serves as a potential biomarker for allergen sensitivity. Under pathological conditions, ENPP3 is overexpressed in various cancers, including renal cell carcinoma, hepatocellular carcinoma, colorectal cancer, and cholangiocarcinoma, making it a potential tumor marker and therapeutic target. ENPP3 is recognized as a major cGAMP hydrolase, which is a second messenger synthesized after the detection of cytosolic double-stranded DNA and is transmitted intercellularly to promote downstream immune signaling. Like ENPP1, ENPP3 inhibits anti-tumor immune responses by hydrolyzing cGAMP.
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