The glycogen cargo receptor STBD1: from biology to disease targeted therapies

Abstract

Glycophagy is a novel selective autophagy characterized by glycogen degradation via the lysosomal enzyme acid α-glucosidase (GAA). Starch-binding domain-containing protein 1 (STBD1) is a glycogen cargo receptor that mediates glycophagy through binding glycogen transport into lysosomes. STBD1-dependent glycophagy has garnered considerable interest in the pathology community, because its dysregulation causes multiple diseases, with cancer being the most serious. Notably, deletions and/or mutations in STBD1 promote tumorigenesis. In this review, we first summarized the current understanding of STBD1, including its structure, subcellular localization, tissue distribution, and biological functions. Next, we examined the roles and molecular mechanisms of STBD1-dependent glycophagy in various diseases (e.g., Pompe disease, Parkinson’s disease, cardiac diseases, and cancer). Based on available research, we discussed the promising function and future of STBD1, including its potential application as a therapeutic target in glycogen-related diseases. We recommend using real-time diagnostic tools to observe the progression of STBD1-mediated glycophagy and gain further insight on the mechanism of action. Such details are needed to investigate new avenues for glycogen-related disease therapy.