Cells use multiple mechanisms to ensure the accurate synthesis of the proteome, including translational and post-translational regulation. My thesis investigates how translation can be modulated to pre-emptively protect against accumulation of aberrant membrane proteins caused by misfolding or secretory pathway disruption. Yor1, the yeast homolog of mammalian CFTR, encodes an ABC transporter that acts as a drug pump to extrude the mitochondrial toxin, oligomycin. A genome wide screen was previously performed in our lab to identify factors that specifically contribute to biogenesis of a misfolded version of this protein, Yor1-F. The main focus of my thesis work is to investigate translation regulators required for Yor1-F biogenesis, in particular the translation initiation repressor, Eap1. Loss of Eap1 significantly impairs synthesis of Yor1-F, whilst loss of the yeast translation initiation factor eIF4G is beneficial. Synthesis defects in eap1 cells can be rescued by reducing ribosome abundance, or by impairing the RQC pathway. This suggests ribosome collisions as a causative factor for reduced Yor1 biogenesis in the absence of Eap1. I further show that mRNAs encoding polytopic membrane proteins globally show low ribosome abundance, with Yor1 amongst the lowest. I propose that cells have evolved to modulate ribosome abundance on transcripts encoding proteins with challenging folding needs in order to reduce the risk of ribosome collisions. I also explored Eap1 function in the context of defects associated with mutations in Sec24, a COPII coat protein that generates ER-derived transport vesicles. Loss of Eap1 and other translation regulators exacerbates various Sec24 growth phenotypes. I further show that translation at the ER is repressed in cells where COPII vesicle formation is impaired by Sec24 mutation and propose that this response from the cell pre- emptively reduces the protein load in the ER to prevent cellular stress. Finally, I move my work into human cells and investigate the impact of knock down of an Eap1 ortholog, 4E-HP, on biogenesis of CFTR, using a flow cytometry assay. Knock down of 4E- HP does not have a detrimental impact on CFTR synthesis, suggesting that 4E-HP is not directly analogous to Eap1 and that mammalian cells likely have a more nuanced approach to regulating ribosome abundance and preventing collisions during translation of transmembrane proteins. Overall, I show that translation in yeast is modulated to manage protein folding and secretory pathway defects, in order to reduce the burden on the ER and enable cell recovery.