Neurotransmitter:sodium symporters (NSS) are integral membrane proteins that mediate the reuptake of monoamine neurotransmitters previously released into the synaptic cleft. They are of pharmacological significance because they are the target of many clinically important drugs. LeuT Aa , a leucine/alanine transporter is a bacterial homolog to NSS. Crystal structures of LeuT Aa with open to outward, occluded and inward-facing states have already been resolved at high resolution. Hence, LeuT Aa serves as a good paradigm for exploring the structure-function relationship of NSS proteins.