Rho GTPases cycle between an inactive GDP and an active GTP bound form which is regulated by positive regulators, GEFs and negative regulators, GAPs and GDIs. Only in their active state, Rho GTPases bind to their downstream effectors and exert their effect on various important biological activities The Rho-associated mental retardation genes are indicated at the appropriate positions. Abbreviations: ALS: amyotropic lateral sclerosis; ARHGEF6, a Rho guanine nucleotide exchange factor 6; FMRP: fragile-X mental retardation-1 protein, GAP: GTPase activating proteins , GDI: guanine nucleotide dissociation inhibitor, GEF: guanine-nucleotide-exchange factor MEGAP, MEntal disorder-associated GAP protein; OPHN1, oligophrenin-1; PAK, p21-activated kinases;