RNF213 Directly Ubiquitylates Glycogen for Quality Control

A study published online in Nature on September 15, 2026, has identified the enzyme RNF213 as playing a direct role in the quality control of glycogen. The research, detailed in the paper "Quality control of glycogen through direct ubiquitylation by RNF213" (doi:10.1038/s41586-026-11139-6), reveals that RNF213 directly attaches ubiquitin molecules to glycogen, a process known as ubiquitylation. This modification is critical for ensuring the integrity and proper function of glycogen, which serves as the primary form of glucose storage in animals and fungi.

Glycogen is a complex carbohydrate that stores energy for rapid release when needed, such as during physical activity or fasting. Maintaining the quality of glycogen is essential for cellular energy homeostasis. Defects in glycogen metabolism or quality control can lead to various metabolic disorders. The study elucidates a novel mechanism by which cells manage glycogen quality, moving beyond previously understood pathways that primarily focused on glycogen synthesis and degradation enzymes.

The enzyme RNF213, also known as a ring finger protein 213, has been previously associated with other cellular processes, including DNA repair and innate immunity. Its identification as a direct ubiquitylating enzyme for glycogen represents a significant expansion of its known functions. Ubiquitylation is a post-translational modification where ubiquitin, a small regulatory protein, is covalently attached to a substrate protein. This modification can signal for protein degradation, alter protein activity, or change protein localization. In this context, the ubiquitylation of glycogen by RNF213 likely serves to mark aberrant or damaged glycogen structures for removal or repair, thereby maintaining a pool of functional glycogen.

This discovery provides new insights into the intricate regulatory networks governing energy metabolism. Understanding how RNF213 specifically targets and modifies glycogen could pave the way for new therapeutic strategies for glycogen storage diseases and other metabolic conditions. The research team's findings offer a molecular basis for how cellular quality control mechanisms extend to complex polysaccharides like glycogen, ensuring efficient energy management within cells. Further investigation into the precise downstream effects of RNF213-mediated ubiquitylation on glycogen structure and cellular fate is anticipated.