Lysosomes have fundamental physiological roles and have previously been implicated in Parkinsons disease(1-5). However, how extracellular growth factors communicate with intracellular organelles to control lysosomal function is not well understood. Here we report a lysosomal K+ channel complex that is activated by growth factors and gated by protein kinase B (AKT) that we term lysoK(GF.) LysoK(GF) consists of a pore-forming protein TMEM175 and AKT: TMEM175 is opened by conformational changes in, but not the catalytic activity of, AKT. The minor allele at rs34311866, a common variant in TMEM175, is associated with an increased risk of developing Parkinsons disease and reduces channel currents. Reduction in lysoK(GF) function predisposes neurons to stress-induced damage and accelerates the accumulation of pathological alpha-synuclein. By contrast, the minor allele at rs3488217another common variant of TMEM175, which is associated with a decreased risk of developing Parkinsons diseaseproduces a gain-of-function in lysoK(GF) during cell starvation, and enables neuronal resistance to damage. Deficiency in TMEM175 leads to a loss of dopaminergic neurons and impairment in motor function in mice, and a TMEM175 loss-of-function variant is nominally associated with accelerated rates of cognitive and motor decline in humans with Parkinsons disease. Together, our studies uncover a pathway by which extracellular growth factors regulate intracellular organelle function, and establish a targetable mechanism by which common variants of TMEM175 confer risk for Parkinsons disease.