OGA (O-GlcNAcase) is a cytosolic and nuclear enzyme that removes O-linked N-acetylglucosamine (O-GlcNAc) moieties from serine and threonine residues of intracellular proteins 1. OGA works in tandem with O-GlcNAc transferase (OGT) to dynamically regulate O-GlcNAcylation, a post-translational modification that controls fundamental cellular processes including signaling, transcription, metabolism, and cell survival 12. The enzyme specifically cleaves GlcNAc but not GalNAc from O-glycosylated proteins and responds to nutrient and stress conditions 1. Dysregulation of OGA activity has significant disease relevance. Reduced OGA levels contribute to cancer progression by promoting hyper-O-GlcNAcylation, which enhances glucose metabolism, proliferation, and drug resistance 34. In hepatocellular carcinoma, OGA degradation leads to increased NF-κB O-GlcNAcylation and anti-apoptotic signaling 5. Conversely, excessive O-GlcNAcylation due to insufficient OGA activity causes cardiomyopathy through mitochondrial dysfunction 6. Clinically, OGA represents a therapeutic target, with enhanced OGA activity showing cardioprotective effects and potential anti-cancer applications 637.