We propose that these genetic perturbations cause the convergent physiological phenotype of steatosis through three separate mechanisms (Figure 7J): (1) transcriptional activation of lipid biosynthesis genes (Insig1 knockout); (2) sequestration of free lipids into droplets (Eif2s1/Aars knockout), possibly as a component of the ISR to protect stressed cells from disruptive lipid molecules88–90; and (3) a distinct Pten-associated mechanism potentially involving blood uptake and increased synthesis, sequestration, and/or repurposing of organellar stores91–94. Here, INSIG1 is linked to steatosis.