Several previous studies have suggested that ENPP1 also contributes to a range of human diseases including diabetes, cancer, cardiovascular disease, and osteoarthritis.
Overproduction of extracellular diphosphate due to hydrolysis of ATP by NPP1 leads to pathological calcium diphosphate (pyrophosphate) dihydrate deposition (CPPD) in cartilage, resulting in a degenerative joint disease that today lacks a cure.
Recently, the ecto-enzyme Enpp1, a suppressor of pathological calcification, was reported to be decreased in joint cartilage with OA in both human and mouse, and <i>Enpp1</i> deficiency causes joint calcification.
TNALP deficiency ameliorates the hypermineralization phenotype in Enpp1(-/-) and ank/ank mice, two models of osteoarthritis and soft tissue calcification.
Nevertheless, the study stimulates interest and will encourage others in the field to test ENPP1 as a possible osteoarthritis susceptibility gene in their cohorts.