Protein synthesis regulation via mammalian target of rapamycin complex 1 
(mTORC1) signaling pathway has key roles in neural development and function, and 
its dysregulation is involved in neurodevelopmental disorders associated with 
autism and intellectual disability. mTOR regulates assembly of the translation 
initiation machinery by interacting with the eukaryotic initiation factor eIF3 
complex and by controlling phosphorylation of key translational regulators. 
Collybistin (CB), a neuron-specific Rho-GEF responsible for X-linked 
intellectual disability with epilepsy, also interacts with eIF3, and its binding 
partner gephyrin associates with mTOR. Therefore, we hypothesized that CB also 
binds mTOR and affects mTORC1 signaling activity in neuronal cells. Here, by 
using induced pluripotent stem cell-derived neural progenitor cells from a male 
patient with a deletion of entire CB gene and from control individuals, as well 
as a heterologous expression system, we describe that CB physically interacts 
with mTOR and inhibits mTORC1 signaling pathway and protein synthesis. These 
findings suggest that disinhibited mTORC1 signaling may also contribute to the 
pathological process in patients with loss-of-function variants in CB.