Manganese (Mn) is an essential metal, but its buildup in the brain at elevated levels causes neurotoxicity. While the crucial role of Mn excretion by the digestive system in preventing Mn neurotoxicity has been well documented for almost a hundred years, the molecular mechanism that controls Mn excretion had been a mystery until the last decade. The necessity of Mn efflux transporter SLC30A10 for preventing Mn toxicity even in the absence of elevated Mn exposure has been reported in animal models and rare human diseases. While SLC30A10's activity in the brain, the liver, and the small intestines is crucial for Mn excretion, the regulation of SLC30A10 expression and activity are yet poorly understood.