Chronic pain affects around one in five of the adult population and has a major negative impact on quality of life. Unfortunately, current treatments are often inadequate due to poor efficacy and tolerability. The molecular causes of chronic pain are not fully defined, hampering efforts to develop alternative therapies. One group of endogenous metabolites proposed to contribute to chronic pain are the polyamines, including putrescine (Put), spermine (Spm), and spermidine (Spd). To date, only intracellular polyamine transport systems have been identified, which include the lysosomal polyamine transporter ATP13A2 (PARK9), which is linked to Parkinson’s disease, and the vesicular polyamine transporters ATP13A3 and SLC18B1 (VPAT), leaving the identity of the plasma membrane polyamine system unknown. Recently, we demonstrated that SLC45A4 encodes a new plasma membrane polyamine transporter, genetically linked to chronic pain in the human population. SLC45A4 offers a new avenue for investigating the regulatory network linking polyamine biosynthesis and transport to neuronal excitability and chronic pain in the human population.