Tsai and colleagues elegantly demonstrate roles for several autism-related molecules including myocyte enhancer factor 2 (MEF2), protocadherin 10 (Pcdh10), and fragile X mental retardation protein (FMRP) in a proteasome-mediated pathway that degrades PSD-95 and leads to synapse elimination (Tsai et al., 2012). Here, FMR1 is linked to autism.