Mutations in regulators and effectors of the Rho GTPases have been found to underlie various forms of intellectual disability (ID), including syndromic and nonsyndromic X-linked forms of ID.Regulators of the Rho GTPases involved in MR include guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs).Among them, oligophrenin-1 (OPHN1) encodes a Rho-GAP and was the first Rho-linked X-linked ID gene identified.