Xdh, also known as xanthine dehydrogenase, is an enzyme that participates in purine metabolism, catalyzing the conversion of hypoxanthine into xanthine and xanthine into uric acid, which is the final steps in purine catabolism [3]. It is present in various organisms, but conversion to xanthine oxidase (XO) only occurs in mammals [1]. Xdh is essential for symbiotically fixed nitrogen assimilation in ureidic legumes and is involved in stress responses in plants and animals [4].

In mice with Xdh-specific depletion in the myeloid cell lineage or Kupffer cells, Xdh loss in monocyte-derived tumor-associated macrophages (TAMs) promoted their M2 polarization and CD8+ T-cell exhaustion, exacerbating hepatocellular carcinoma (HCC) progression [2]. In C. elegans, inactivation of Xdh-1 caused xanthine stone formation, and a forward genetic screen uncovered that mutations in sulp-4 enhanced the penetrance of xanthine stone formation in Xdh-1 null mutant C. elegans [3].

In conclusion, Xdh is crucial for purine metabolism. Gene-knockout models in mice and C. elegans have revealed its role in processes like macrophage polarization in HCC and xanthine stone formation. These findings contribute to understanding the mechanisms underlying certain diseases, potentially providing new insights for treatment strategies in related disease areas such as cancer and urolithiasis.