NYAP2 (neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2) is an adaptor protein that links PI3K signaling to actin cytoskeleton remodeling in developing neurons. NYAP2 functions as a molecular bridge by simultaneously binding to PI3K p85 and the WAVE1 complex, thereby recruiting WAVE1 to sites of PI3K activation 1. Upon stimulation, NYAP2 becomes tyrosine phosphorylated by Fyn kinase and activates the PI3K-Akt-Rac1 signaling cascade, which promotes actin remodeling through WAVE1-mediated cytoskeletal changes 1. This coordinated signaling is essential for regulating neuronal morphogenesis, including neurite elongation, as demonstrated by the effects of NYAP gene disruption on brain size and neurite development in mice 1. Beyond neuronal development, NYAP2 variants show association with insulin sensitivity in genome-wide association studies, though this association appears dependent on the IRS1 locus 2. Additionally, NYAP2 has been implicated in autism spectrum disorder pathogenesis, identified as part of copy number variations in affected populations and functioning within the Contactins-NYAPs-WAVE1 pathway 3. NYAP2 also serves as a substrate for protein tyrosine phosphatase PTPRZ and participates in oligodendrocyte differentiation through PI3K-AKT pathway activation 4.