Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and there is no cure to treat or prevent the disease. The cardinal motor symptoms of PD are caused by a decline of nerve cells producing the neurotransmitter dopamine, which is necessary for the initiation of voluntary movements, but other transmitter systems including the serotonin and norepinephrine systems are affected as well and are related to non-motor symptoms such as depression and dementia. On a pathological level, PD is also characterized by intracellular proteinaceous inclusions known as Lewy bodies that contain the misfolded and aggregated protein alpha-synuclein (ASYN). Despite decades of ASYN research, the actual physiological role of ASYN is still not well understood. Among a plethora of different cellular functions, ASYN has been proposed to directly interact with the transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT), but the physiological effects of these interactions remain unclear. Here, we investigated the interaction of ASYN with DAT, SERT and NET on transport activity and transporter expression. We find that overexpression of ASYN (but not the closely related beta- or gamma-synucleins) using various heterologous expression systems led to increased transport rates and elevated transporter expression. In contrast, siRNA-induced knockdown of endogenous ASYN or CRISPR/Cas9-mediated knockout of the SNCA gene led to reductions in DAT- and SERT-mediated substrate uptake and transporter expression. We are currently investigating the molecular mechanisms underlying these effects in cells, primary cultures and in vivo.