SPPL3 and cancer: Recently, cancer cells subjected to selection for increased or decreased expression of MHC-I have been subjugated to forward genetic screenings, identifying a substantial number of new genes that are able to regulate MHC-I antigen presentations, including IRF2, PBAF, PRC2, and SPPL3 (Kriegsman et al., 2019; Patel et al., 2017; Burr et al., 2019; Chang et al., 2005; Manguso et al., 2017; del Campo et al., 2009; Del Campo et al., 2014; Garcia-Lora et al., 2003; del Campo et al., 2014).