E490del drastically increased early expression of ENPP1, TNAP and PIT-1 and corresponding ENPP1 activity as compensation for lack of ANKH at the cell membrane, however as this mutant did not completely abolish ANKH localisation and hence, the compensatory effect seemed to be overpowered and might indeed be causal in the pathogenesis of CPPDD in sufferers affected by the E490del mutation, requiring further study. This evidence concerns the gene SLC20A1 and chondrocalcinosis 2.