Significance Intellectual disability associated with Oligophrenin 1 (OPHN1) mutation is a neurodevelopmental disorder characterized by a wide range of cognitive and social dysfunction. Here, we dissected the impact of OPHN1 mutation on the postnatal migration of inhibitory interneurons, a process that is thought to play a key role in postnatal developmental plasticity. We found that loss of function of OPHN1 led to an early maturation of the morphofunctional properties of the neuronal precursors that impaired their migration and resulted in a dramatically lower number of cells reaching their target area. We identified pharmacological treatments able to rescue the abnormal development of neuronal precursors and their migration.