The intricate relations between these pro- and anti-calcification mediators have been well-documented in, e.g., murine and human PXE, with low serum levels of MGP and Fetuin-A, contributing to the upregulation of RUNX2 through the BMP2-SMAD-RUNX2 and TGFB2-SMAD2/3 pathways [128,138,145,146,147,148] but also affecting the calcification propensity T50 test, which reflects the time required to convert 50% of primary CPPs in a serum sample into secondary CPPs [149,150,151]. Here, SMAD2 is linked to Pseudoxanthoma elasticum.