Interestingly, Cho et al. revealed that the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1 to the Notch-responsive elements (NREs) on the Rheb promoter is a key event, was the main mechanism behind the generation of the multiple lineages present in angiomyolipoma [109]. The gene discussed is RHEB; the disease is angiomyolipoma.