GAPDH is a multifunctional enzyme best known for catalyzing the conversion of glyceraldehyde-3-phosphate to 3-phospho-D-glyceroyl phosphate in glycolysis and gluconeogenesis 1. Beyond its canonical metabolic role, GAPDH possesses nitrosylase activity enabling post-translational modifications of nuclear proteins like SIRT1 and HDAC2 1. GAPDH assembles into the GAIT complex upon interferon-gamma treatment, selectively suppressing translation of inflammatory mRNAs by binding GAIT elements in their 3'-UTRs 2. It promotes innate immune responses through TRAF2 and TRAF3 interactions, activating NF-κB and type I interferon production 3. GAPDH compartmentalizes to specific cellular locations including the nucleus, where it participates in transcription, DNA replication, and apoptosis 4. Post-translational modifications regulate GAPDH function: S-nitrosylation inactivates SIRT1 deacetylase, promoting tau acetylation implicated in neurodegeneration after traumatic brain injury 5; succinylation at K251 increases GAPDH stability and enhances glycolysis in lung cancer cells exposed to cigarette smoke 6; and acetylation at Lys84/86/227 promotes T-cell glycolytic metabolism and activation 7. The GAPDH active-site cysteine redox switch provides critical oxidative stress protection in tumor cells 8. These functions extend far beyond glycolysis, establishing GAPDH as a metabolic-immunological nexus with therapeutic implications for cancer and inflammatory diseases.