TNFR1 activates NF-κB through cascades of polyubiquitination that culminate in the activation of IKK and phosphorylation of IκBα responding to TNF (Peltzer et al., 2016; Jean-Charles et al., 2018), and ubiquitin-specific protease 20 (USP20) would deubiquitinate RIPK1 and alleviate TNF and IL-1β-evoked atherogenic signaling in SMCs accordingly, which add to the evidence demonstrating that SMC-specific gene expression affects atherosclerosis (Subramanian et al., 2010; Liu D. et al., 2016; Jean-Charles et al., 2018). The gene discussed is USP20; the disease is atherosclerosis.