In essence, this elegant work addresses the three main challenges of the FXS field by: (1) developing a Fmr1 knockdown stem cell model that allows study of the earliest events of neurogenesis to support NBS and early intervention; (2) identifying a role for APP in the kinetics of neurogenesis, which supports the development of APP metabolites as potential FXS biomarkers; and (3) demonstrating rescue of shFmr1 mESC morphology with a BACE-1 inhibitor thus promoting study of APP and secretases as therapeutic targets for FXS. The gene discussed is FMR1; the disease is fragile X syndrome.