For example, hemimegalencephaly, characterized by the abnormal enlargement of a cerebral hemisphere, is caused by obligatory somatic mutations that abnormally activate the mammalian target of rapamycin (mTOR) pathway, such as gain-of-function mutations in MTOR or its upstream positive regulator AKT3 as well as loss-of-function mutations in its upstream negative regulator DEPDC5 [37,38,39,40]. Here, MTOR is linked to hemimegalencephaly.