Although low bone mass has been described in several murine models of Enpp1 deficiency, including ttw mice (33), ENPP1 knockout (KO) mice (Enpp1−/−) (97), and an ENPP1 C397S mutant mouse discovered as part of a large genome-wide mutagenesis screen to identify genes regulating bone mass (98), osteoporosis in ENPP1-deficient patients had not been noted until recently. The gene discussed is ENPP1; the disease is osteoporosis.