At present, not only the A2A receptor (A2AR) is at the center stage for increasing the therapeutic tools in a variety of clinical indications, but this opinion paper focuses on the A2AR antagonists, which shows promise in immune-mediated control of cancer progression (10–13), in atrial fibrillation (14, 15), and in fighting against neurodegenerative diseases (see later). Here, ADORA2A is linked to neurodegenerative disease.