Catecholaminergic signaling regulates various physiological functions, such as blood pressure, and its termination involves sodium-driven neuronal reuptake and a corticosterone-sensitive, low-affinity, high-capacity extraneuronal transport system (uptake2). Here we report the molecular identification and pharmacological characterization of the extraneuronal catecholamine transporter (EMT), a new member of the amphiphilic solute facilitators (ASF) family, cloned from human Caki-1 kidney carcinoma cells using degenerate primers targeting ASF sequence motifs. EMT consists of 556 amino acids with 12 putative transmembrane segments. Functional studies in EMT-transfected 293 cells demonstrated it mediates uptake of catecholamines (adrenaline, noradrenaline, tyramine), 5-hydroxytryptamine, and the neurotoxin MPP+ with kinetic properties (Km ~510 µM for noradrenaline, Vmax ~3.9 nmol/min per mg protein) matching extraneuronal transport. EMT is sensitive to corticosterone and disprocynium24 (extraneuronal transport inhibitors) but resistant to desipramine (neuronal noradrenaline transporter inhibitor) and reserpine (vesicular transporter inhibitor). RT-PCR revealed EMT mRNA in human liver, heart, and brain cortex, consistent with broad tissue distribution. Fluorescence in situ hybridization mapped the EMT gene to chromosome 6q27, a region linked to type 1 diabetes susceptibility. EMT acts as a second line of defense to inactivate monoamines escaping neuronal reuptake, with potential roles in autonomic dysfunction, neuropsychiatric disorders, and glucose homeostasis.