SLC45A4 is a neuronal polyamine transporter with critical roles in pain perception and metabolic regulation. Primarily, it functions as a selective plasma membrane transporter of polyamines including putrescine, cadaverine, spermine, and spermidine 1. The protein is enriched in sensory neuron subtypes within the dorsal root ganglion, where it regulates C-polymodal nociceptor excitability through polyamine-mediated modulation of neuronal signaling 1. Genome-wide association studies identified SLC45A4 variants as significantly associated with chr8 pain intensity in human populations 12. Mice lacking SLC45A4 demonstrate normal mechanosensitivity but reduced sensitivity to noxious heat and algogen-induced tonic pain due to decreased nociceptor excitability 12, establishing polyamine transport as essential for pain perception. Beyond neuronal function, SLC45A4 demonstrates additional metabolic activities. It functions as an H+-dependent sugar cotransporter promoting glycolysis in cancer cells, contributing to malignant progression in ovarian and pancreatic cancers 34. Additionally, SLC45A4 localizes to peroxisomal membranes where it transports putrescine to promote GABA de novo synthesis via the Arginine/Ornithine/Putrescine pathway 5. Clinically, SLC45A4 represents a promising therapeutic target for pain management and potential cancer intervention strategies.