Glce, also known as D-glucuronyl C5-epimerase, is a crucial enzyme in heparan sulfate (HS) biosynthesis. It converts D-glucuronic acid to L-iduronic acid, increasing HS flexibility, which is important for protein-ligand recognition. HS is involved in many physiological processes such as embryonic development, cell growth, and inflammation [3].

In hepatic Glce-knockout mice fed a high-fat diet, Glce deficiency led to impaired thermogenesis in adipose tissue and exacerbated obesity. This was associated with decreased levels of growth differentiation factor 15 (GDF15) in Glce-knockout mouse hepatocytes, as liver Glce deficiency reduced the production and increased the degradation of mature GDF15, perturbing lipid homeostasis [1]. In Glce-deficient mice, there were increased regions of proliferating chondrocytes in endochondral bones along with a delayed onset of hypertrophic differentiation, and elevated Indian hedgehog (Ihh) signaling due to altered HS structure [2].

In conclusion, Glce is essential for the proper synthesis of HS and plays a role in multiple biological processes. Studies using Glce-knockout mouse models have revealed its significance in lipid metabolism and obesity, as well as in endochondral ossification. These findings provide insights into potential therapeutic targets for obesity and understanding the mechanisms of endochondral bone development [1,2].