NSI-189 is a benzylpiperizine-aminiopyridine, a novel chemical entity that stimulates neurogenesis of human hippocampus-derived neural stem cells in vitro and stimulates neurogenesis in murine hippocampus in vivo. Emerging evidence also shows that NSI-189 phosphate has regionally specific effects insofar as neurogenesis is observed largely in the subventricular zone of the hippocampus. Results from a preliminary proof of concept study suggests that NSI-189 may be capable of mitigating depressive symptoms and improve cognitive function in adults with DSM-5-defined Major Depressive Disorder (MDD). Primary proof-of-concept studies show both antidepressant and procognitive effects. Beneficial effects in cognitive-emotional processing as well as whether the procognitive effects are independent of antidepressant effects are vistas of future research. Taken together, NSI-189 is a multi-domain neurogenic compound with brain-therapeutic properties with potential therapeutic applications across disparate psychiatric disorders.