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Glucose-regulated protein 78 (GRP78) is an important chaperone protein that is predominantly expressed in the endoplasmic reticulum. The multifunctional roles of GRP78 in protein folding, endoplasmic retic-ulum calcium binding, cytoprotection, and anti-apoptosis, as well as its function as a receptor on the cell surface, disclose its major involvement in physiological and numerous pathological conditions. Recent advances in mouse models targeting GRP78 allele have revealed the essential roles of GRP78 in development and neurological disorders, as well as accurate neural migration and neuroprotection. This review of correlation between GRP78 and embryogenesis and neurological disorders provides further directions for investigation, as well as potential therapeutics for clinical use.