Given the link between Gα12/13, PLD activation and the important role of PLD in long-term depression in the prefrontal cortex, further work to determine whether or not the M1 mAChR biased allosteric modulators can selectively activate Gα12/13 signaling pathways may provide vital information regarding the direction for the development of future M1 mAChR targeted therapeutics. This evidence concerns the gene GPLD1 and major depressive disorder.