CNTNAP2 is cleaved by matrix metalloproteinase 9 (MMP9), and the shed ectodomain regulates Ca2+ homeostasis and neuronal network synchrony.30 Recently, we found that CNTNAP2 is cleaved by presenilins-dependent γ-secretase to produce the CNTNAP2 intracellular domain (CICD), and expression of the CICD improves autism-like behaviors.31 Our current study reveals that in addition to its γ-secretase cleavage, CNTNAP2 undergoes complex proteolytic processing by furin and a disintegrin and metalloproteinase (ADAM)10/17-dependent α-secretase. This evidence concerns the gene ADAM10 and autism.