A large body of evidence has linked the PACAP/PAC1R system to protective functions in the nervous and immune systems, as well as to stress- and anxiety-related behaviors (in particular post-traumatic stress disorder), migraine, nociception, thermoregulation, sleep/wake cycles, and reproductive functions (Dickson and Finlayson, 2009; PACAP, 2016; Biran et al., 2020), making it a peptide signaling system of high clinical relevance. This evidence concerns the gene ADCYAP1 and migraine disorder.