Previously we have shown that mutations in Alkaptonuria result in the inactivation of homogentisate 1,2-dioxygenase (HGD) by several mechanisms, including through destabilisation of the protomer, by preventing formation of the active hexamer, or by interfering with its active site leading to alteration of substrate recognition or catalytic activity1, 2. Here, HGD is linked to alkaptonuria.