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, which increases HS flexibility and is important for protein ligand recognition. HS is involved in numerous physiological processes such as embryonic development, cell growth, inflammation, and blood coagulation [3].

In hepatic Glce-knockout mice fed a high-fat diet, Glce deficiency led to impaired thermogenesis in adipose tissue and exacerbated obesity. Hepatic Glce deficiency also decreased the production and increased the degradation of mature growth differentiation factor 15 (GDF15), reducing its secretion. This shows that the Glce-GDF15 axis is important in maintaining energy balance and lipid homeostasis [1].

In Glce-deficient mice, there were increased regions of proliferating chondrocytes and a delayed onset of hypertrophic differentiation in endochondral bones, along with elevated Indian hedgehog (Ihh) signaling, indicating that Glce-regulated HS structure is critical for Ihh distribution and signaling in chondrocytes [2].

In conclusion, Glce is essential for HS biosynthesis and impacts multiple biological processes. Studies using Glce-knockout mouse models have revealed its role in obesity and endochondral ossification, highlighting its importance in maintaining energy balance and skeletal development.