Mutations causing monogenic autism define an axis of synaptic pathophysiology. Recent data suggest that proper synaptic function requires an optimal level of mGluR-regulated protein synthesis and that deviations in either direction can produce similar impairments in cognitive function (Auerbach et al. 2011). Two types of monogenic autism, TSC and FXS, lie on opposite ends of this spectrum and, correspondingly, show reduced and increased protein synthesis rates, and respond to opposite alterations in mGluR5 activation (PAM and NAM, respectively). Abbreviations: FXS, fragile X syndrome; mGluR, metabotropic glutamate receptor; NAM, negative allosteric modulator; PAM, positive allosteric modulator; TSC, tuberous sclerosis complex; WT, wild type.