(A) Schematic of major Trio isoforms present in the adult mouse brain, with locations of engineered neurodevelopmental disease (NDD)-associated Trio variants: K1431M is a rare missense variant in the GEF1 DH domain associated with autism spectrum disorder (ASD); a K1918X nonsense variant that lies just before the GEF2 domain associated with schizophrenia (SCZ); and M2145T missense variant in the GEF2 DH domain found in an individual with bipolar disorder (BPD). Here, TRIO is linked to autism spectrum disorder.