More recently, another pathway has been proposed, related to fibrosis of the atrial myocardium and AF pathogenesis, involving reduced uptake of Ca2+ ions from the cytosol by the mitochondria in a profibrotic environment, which increases Ca2+ concentration and further promotes Ca2+ signaling pathways involving pathological overactivation of cardiac type 2 ryanodine receptors (RyR2) and increased oxidative stress, which fuels NLRP3 inflammasome activation [Figure 3]. The gene discussed is NLRP3; the disease is atrial fibrillation.