Here, using cancer cell lines with different degrees of GCN2 dependency as experimental models, we show that GCN2 plays a key role in regulating the cellular proteome in a manner that is independent of the ISR (Figs 2A, B, and E and S2A and B), results that are supported by our observations that the ISR inhibitor ISRIB had no relevant effect on the viability or transcriptome of GCN2-dependent cells (Figs 2F and S2B and C). The gene discussed is EIF2AK4; the disease is cancer.