Assembly of the PANoptosome is triggered by diverse cellular stresses or pathogenic stimuli, with key upstream sensors -including AIM2, RIPK1, ZBP1 and NLRP12 – nucleating distinct complexes: the AIM2-PANoptosome in response to herpes simplex virus 1 and Francisella novicida [21]; the RIPK1-PANoptosome during Yersinia infection [22]; theZBP1-PANoptosome in influenza A virus infection infection [23]; and the NLRP12-PANoptosome in hemolytic diseases such as malaria and sickle cell disease [24]. The gene discussed is NLRP12; the disease is sickle cell disease.