Stbd1, short for Starch-binding domain-containing protein 1, is a glycogen-binding protein that plays a pivotal role in cellular energy metabolism [1]. It is involved in processes such as glycophagy, glycogen accumulation, and lipid droplet formation, and is associated with pathways related to autophagy and glucose metabolism [1]. Given its significance in energy-related processes, understanding Stbd1 is crucial for deciphering physiological processes and developing disease therapies.

Stbd1-deficient (Stbd1KO) mice have been instrumental in uncovering its functions. Stbd1KO mice at 24 weeks showed reduced hepatic glycogen content, aberrant glucose homeostasis, and insulin resistance, along with enhanced ER-mitochondria association and mitochondrial fragmentation in the liver [2]. This indicates a role for Stbd1 in maintaining the integrity of hepatic mitochondria-ER contact sites (MERCs) and controlling glucose metabolism [2]. In another study, Stbd1 overexpression in an in vitro hepatocyte model enhanced cellular sensitivity to insulin and improved insulin resistance, by activating the AMP-activated protein kinase (AMPK) signaling pathway, independent of N-myristoylation and related changes in ERMCs, glycogen levels, etc. [3].

In conclusion, Stbd1 is essential for maintaining glucose homeostasis, with its function in glycogen metabolism and autophagy-related processes. The use of Stbd1KO mouse models has revealed its significance in insulin resistance and glucose metabolism-related diseases, providing valuable insights into potential therapeutic strategies targeting these conditions.