"Abstract. Background: Microgravity is a physical force that affects cellular functions, including gene expression, cellular differentiation, proliferation, and signal transduction. Ion channels play an important role in ionic permeability and cell physiology. In addition, ion channels have been shown to contribute to volume regulation, fluid homeostasis, blood pressure regulation, mechanosensation, and cell migration. The lipid composition and fluidity of the plasma membrane of various cell types contribute to the regulation of ion channels. We hypothesized that protein expression of acid-sensing ion channels (ASICs) is decreased while membrane fluidity is increased, leading to delayed activation of human platelets subject to microgravity conditions. Methods and Results: Platelets were maintained in simulated microgravity conditions using the rotating wall vessel method. Thromboelastography analysis showed there is a delay in platelet activation in human platelet samples subject to simulated microgravity conditions compared to normal gravity for 5 days at 37 °C. Western blotting and immunofluorescence microscopy studies showed that ASIC1/2 proteins are significantly downregulated in human platelets subject to the same simulated microgravity conditions. In addition, membrane fluidity was increased while sphingomyelin concentration was decreased in human platelets subject to simulated microgravity compared to normal gravity conditions. Conclusions: Taken together, the data from this study suggest that simulated microgravity delays platelet activation in human platelets in a mechanism presumably involving a decrease in ASIC1/2 protein expression and sphingomyelin plasma membrane concentration."