SHANK3 and nervous system disorder: Indeed, like all SHANK proteins, SHANK3 contains multiple domains for extensive protein-protein interaction including ankyrin (ANK) repeats—hence a deficit in these central and major cytoskeletal components, key players for both synapse formation and the modulation of synaptic transmission and synaptic plasticity, may be responsible for major synaptic aberrations and loss of the capability for inter-neuronal communication, with ensuing cognitive impairment, as has been observed in multiple neurological disorders (9, 10, 12) (Figures 1A–E).