Strong genetic linkage was found with mutations in the "ABCC6" gene, which codes for the ABCC6 protein, which is a membrane transporter from the large ATP-binding cassette transporter family. The protein is expressed in most organs, but mainly in the liver and kidney. ABCC6 mediates ATP release in the liver. This is the main source of circulating pyrophosphate (PPi), and individuals affected by PXE have strongly reduced plasma PPi levels, explaining their mineralization disorder. One study suggested that mutations causing total absence of an ABCC6 protein caused a more severe disease, but this could not be confirmed in a subsequent case series. Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic, environmental, and lifestyle) may be involved.