As for an underlying mechanism in the clinical phenotypes, disrupted actin regulation caused by aberrant Rac/Cdc42-PAK1 signaling was supposed to be a core event; hampered actin reorganization gives rise to abrogated neurite growth and spine formation, which are relevant to the pathophysiology of ID and microcephaly in PLEKHG2-associated neurological disorder. The gene discussed is PAK1; the disease is nervous system disorder.