RNF213 and Moyamoya disease: To pinpoint the E3 enzyme responsible for the ubiquitylation of LPS, Otten and colleagues executed a procedure of extensive fractionation and purification of the HeLa cell lysates and tested each fraction for the E3 activity that is responsible for LPS ubiquitylation, leading to the identification of RNF213 (Figure 1), an E3 that is known to be connected to the moyamoya disease.