Given the established roles of RGS12 in modulating KOR signaling (i.e., dampening G protein output but enhancing β-arrestin recruitment), particularly within the dopamine-rich environments of the ventral striatum [23,24], any disruption caused by a BD-associated missense mutation may exacerbate the dynorphin-mediated effects in stress responses. Here, OPRK1 is linked to Behcet disease.