ENPP2

This gene encodes a secreted lysophospholipase D that hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA), a signaling molecule involved in cell proliferation, migration, and angiogenesis. Biallelic mutations cause generalized arterial calcification of infancy (GACI), a severe autosomal recessive disorder presenting in early infancy with calcification of large arteries and cardiac complications. The gene shows high tolerance to loss-of-function variants (low pLI score), consistent with its recessive inheritance pattern.