It has been suggested that decreased or absent FMRP disrupts normal DAGL trafficking and the formation of functional postsynaptic group I metabotropic glutamate receptor 5 (mGluR5)-DAGL complexes and disables on-demand endocannabinoid release and retrograde signaling in FXS, leading to ectopic production of 2-AG [27]. Here, GRM5 is linked to fragile X syndrome.