Identification of the PI3K p110ß subunit and PI3K activator PIKE as direct targets of FMRP may explain elevated PI3K signalling in FXS17, 24, 37, whereas how the loss of FMRP-dependent translation suppression leads to elevated ERK1/2 signalling in FXS has remained mysterious. The gene discussed is AGAP2; the disease is fragile X syndrome.