First, unlike its counterparts, the PI3K/Akt/mTOR cascade is a primary downstream effector of insulin and insulin-like growth factor (IGF) signaling 15, positioning it as a direct molecular “sensor” for the hallmark metabolic disturbances of MASH—namely, IR and the resultant chronic hyperinsulinemia 10. The gene discussed is INS; the disease is Hyperinsulinemia.