A new systematic review confirms that erinacines, neuroactive compounds from lion’s mane (Hericium erinaceus), consistently support brain health across preclinical models. Erinacine A, the most studied, stimulated nerve growth factor (NGF), reduced inflammation, protected against brain cell death, and improved memory in models of Alzheimer’s, Parkinson’s, stroke, and depression. This is the strongest synthesis to date of how lion’s mane compounds protect the brain at the cellular and behavioral level.