Mutations in PTEN, which encodes a PtdIns(3,4,5)P3 phosphatase, and in TSC1 and TSC2, which are key effectors in the PtdIns(3,4,5)P3 signaling pathway, have demonstrated the importance of synaptic phosphoinositide signaling in syndromic forms of autism (Figure 3) [9,34,35]. This evidence concerns the gene PTEN and autism.