Pituitary adenylate cyclase-activating polypeptides (PACAPs) were discovered in the 1980s in the process of searching for unknown hypothalamic factors after the successive discovery of hypophysiotorpic hormones such as TRH, GHRH, and CRH. PACAP38, consisting of 38 amino acids, and PACAP27, consisting of 27 residues at its N-terminus, were isolated and identified from sheep hypothalamic extracts in 1989 using the stimulatory activity of cyclic AMP production in rat pituitary cells. Their structures show 68% homology to vasoactive intestinal peptide (VIP) and belong to the secretin-glucagon family. PACAP38 is widely distributed in the brain, with the highest concentration in the hypothalamus, where it promotes the secretion of almost all pituitary hormones. PACAP38 is widely distributed in the brain and is found in highest concentration in the hypothalamus, but it promotes the secretion of almost all pituitary hormones, and its full physiological function in the hypothalamus has yet to be elucidated. However, focusing on its function as a neurotrophic factor, we aim to apply it clinically as an agonist in the treatment of ischemic brain diseases such as stroke and neurodegenerative diseases. In the meantime, research is being conducted on the clinical application of antagonists for the treatment of intractable pain based on their function in pain transmission as neurotransmitters.