GSN and familial dilated cardiomyopathy: Taken together, these results highlight a key regulatory role of the PI3Kα-gelsolin complex in mechanotransduction, with the marked decrease in p110α levels in human and canine DCM hearts further suggesting a causal role in HF most likely due to a reduced PIP3-mediated suppression of gelsolin activity (Fig. 5f, g and Supplementary Data 1).