GYG2 encodes glycogenin-2, an X-linked protein that participates in glycogen biosynthesis by initiating primer formation for glycogen synthesis 1. Unlike its paralog GYG1, GYG2 exhibits minimal autoglycosylation activity and functions as a suppressor of glycogen formation, with both glycogenins coordinating glycogen synthase activity in a cell-type-dependent manner to maintain glucose homeostasis 2. GYG2 is subjected to X chromosome X in normal human fibroblasts 3, localizing to Xp22.3 near the X-Y pseudoautosomal region 1. Functionally, GYG2 is not essential for liver glycogen synthesis or glucagon-stimulated glucose release, as individuals with complete GYG2 deletions show normal glucose metabolism and liver histology 4. However, disease-causing mutations are clinically significant: a hemizygous missense mutation (W222S) impairs self-glucosylation and associates with Leigh syndrome in males 5. Additionally, GYG2 emerges as a novel aging biomarker in subcutaneous adipose tissue linked to mitochondrial function 6, and recent evidence suggests GYG2 suppresses glioma cell apoptosis, making it a potential oncolytic virus therapy target 7. GYG2 has been identified as a candidate disease gene in rare genetic disorders 8.