These observations suggest that different frequencies for occurrence of the Y451C variant could explain the 10–40 times higher prevalence of OPLL in the Japanese population (1.8–6.4%) as compared with the US (0.12%) and German (0.1%) populations (91, 92), observations suggesting that ENPP1 pathogenic variants may be driving the enthesopathies in a subset of DISH and OPLL patients. Here, ENPP1 is linked to ossification of the posterior longitudinal ligament of the spine.