ENPP1 (human, recombinant)

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) is a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzyme activities.¹ It is expressed in skeletal, adipose, hepatic, renal, cardiac, and placental tissues, as well as pancreatic islets, salivary glands, chondrocytes, fibroblasts, and lymphocytes.² ENPP1 is a critical regulator of purinergic signaling that catalyzes the hydrolysis of ATP or GTP to AMP or GMP, respectively, as well as the hydrolysis of cGAMP, and has roles in platelet aggregation, muscle contraction, hypoxia, ischemia, cGAS-STING signaling, and cell proliferation, migration, apoptosis, and differentiation.^1,3 This nucleotide hydrolysis also generates inorganic pyrophosphates, which inhibit bone and cartilage mineralization, implicating ENPP1 as a regulator of bone and cartilage development. Loss-of-function mutations in ENPP1 are associated with various calcification-related disorders, including autosomal recessive hypophosphatemic rickets type 2 (ARHR2) generalized arterial calcification of infancy (GACI), and pseudoxanthoma elasticum (PXE).^1,4 ENPP1 SNPs are associated with insulin resistance and the development of diabetic nephropathy.^2,5 ENPP1 hydrolysis of cGAMP in the tumor microenvironment decreases STING activation, facilitates immunosuppression, and is associated with enhanced bone metastasis in mouse xenograft models of breast cancer.^1,3 Inhibition of ENPP1 promotes STING activation and increases survival in various mouse xenograft models.¹ Cayman’s ENPP1 (human, recombinant) protein can be used for enzyme activity assays.

WARNING This product is not for human or veterinary use.

1. Onyedibe, K.I., Wang, M., and Sintim, H.O. ENPP1, an old enzyme with new functions, and small molecule inhibitors - A STING in the tale of ENPP1. Molecules 24(22), E4192 (2019).

2. Sortica, D.A., Crispim, D., Zaffari, G.P., et al. The role of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 in diabetic nephropathy. Arq. Bras. Endocrinol. Metab. 55(9), 677-685 (2011).

3. Li, L., Yin, Q., Kuss, P., et al. Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs. Nat. Chem. Biol. 10(12), 1043-1048 (2014).

4. Bowman, M.A.H., and McNally, E.M. Genetic pathways of vascular calcification. Trends Cardiovasc. Med. 22(4), 93-98 (2012).

5. Bacci, S., De Cosmo, S., Prudente, S., et al. ENPP1 gene, insulin resistance and related clinical outcomes. Curr. Opin. Clin. Nutr. Metab. Care 10(4), 403-409 (2007).