GTPases are involved in a wide variety of functions ranging from vesicular trafficking, membrane transport, actin networking, etc., In the human brain, small GTPases are involved in the regulation of various functions such as phagocytosis and vesicular trafficking by Rab and Arf family of GTPases in microglia; actin remodelling and microglial migration by Rho GTPases; maturation of dendritic spines and neuronal survival by Rho GTPases, etc. The signaling of these different GTPases and their pathological role in Alzheimer’s disease have been widely described. The gene discussed is CDKN2A; the disease is Alzheimer disease.