GPD1 (glycerol-3-phosphate dehydrogenase 1) is a cytosolic NAD+-linked enzyme that catalyzes the conversion of dihydroxyacetone phosphate to glycerol-3-phosphate, serving as a critical component of the glycerol-3-phosphate shuttle system 1. Together with mitochondrial GPD2, GPD1 functions as an NADH shuttle for mitochondrial bioenergetics and acts as an important bridge between glucose and lipid metabolism 1. The enzyme plays a key role in managing cellular redox balance by consuming NADH and attenuating reductive stress, particularly under hypoxic conditions 2. GPD1 forms complexes with other metabolic enzymes including aldolase B and GPD1L to facilitate glycerol biosynthesis and excretion 2. Clinically, GPD1 has emerged as a significant therapeutic target across multiple diseases. In bladder cancer, GPD1 acts as a tumor suppressor by promoting apoptosis through the lysoPC-PAFR-TRPV2 axis, with pharmacological activation showing therapeutic potential 3. Conversely, in castration-resistant prostate cancer, GPD1 promotes tumor progression through cell cycle regulation and sphingosine 1-phosphate metabolism 4. GPD1 also contributes to ferroptosis resistance in gastric cancer by facilitating lipid droplet accumulation 5. Additionally, GPD1 serves as a metformin target associated with healthy aging biomarkers 6.