DAB1

Disabled-1 (DAB1), alternatively named DAB or DAB-1, is a core downstream effector in the reelin signaling pathway. It transduces intracellular signals upon reelin binding to VLDLR and ApoER2 receptors. Phosphorylation of DAB1 by Src family kinases modulates cytoskeletal dynamics, essential for neuronal migration and laminar organization during brain development.
Impaired DAB1 function contributes to Type 1 lissencephaly, a neurodevelopmental disorder marked by smooth cerebral cortex. It also correlates with autism spectrum disorders and schizophrenia. Drug development targeting the reelin-DAB1 axis remains preclinical, with small molecules and gene therapies under investigation to rectify neuronal migration defects, but no clinical candidates exist to date.