Experimental data show that K-Ras, regardless of mutation status, activates its downstream effectors primarily at the inner PM leaflet, and that dissociating K-Ras from the PM blocks K-Ras signal output and the growth of K-Ras-driven cancers (Cho et al, 2012b, 2016a, 2016b; van der Hoeven et al, 2013; Kattan et al, 2019, 2021; Miller et al, 2019; Tan et al, 2019; Garrido et al, 2020; Kovar et al, 2020). This evidence concerns the gene KRAS and cancer.