Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a highly conserved enzyme in the glycolytic pathway, also acts as a moonlighting protein, performing various functions beyond its classical role in glycolysis, such as regulating gene expression, participating in cell signal transduction, and responding to environmental stress. By interacting with various signaling molecules, GAPDH plays a regulatory role in hormone signaling pathways, influencing plant growth and development. Functional plasticity in GAPDH is modulated mainly through redox-driven post-translational modifications, which alter the enzyme's catalytic activity and influence its subcellular distribution. This review explores the diverse functionalities of GAPDHs in plants, highlighting their significance in plant metabolic processes and stress adaptation.