Structural Model of the Endosomal Commander Complex: Implications for X-Linked Intellectual Disability and Ritscher-Schinzel Syndrome

A recent study published in Cell by Healy et al. describes a new structural model of the endosomal Commander complex created using a combination of X-ray crystallography, Cryo-EM, Alphafold predictions, and site-directed mutagenesis. This model provides insights into the molecular characteristics of this evolutionarily-conserved protein machinery. Importantly, the study identifies mutations that are responsible for X-linked intellectual disability (XILD) and Ritscher-Schinzel syndrome (RSS). The findings have significant implications for understanding the molecular basis of these disorders and developing potential treatments.