ER’s multi-trick pony

Cells constantly adjust protein production to match folding capacity in the endoplasmic reticulum (ER) to ensure correct folding of secreted and transmembrane proteins. This is especially crucial when cellular stress impairs protein folding. In a new study from the Karagöz lab, published in Genes & Development, first author Aleksandra Anisimova uncovers how the RNA-binding protein IGF2BP3 helps control this balance during ER stress. The study reveals a flexible regulatory system that balances mRNA decay with transcriptional control to fine-tune the unfolded protein response (UPR), highlighting a previously underappreciated layer of post-transcriptional control that determines whether cells adapt or fail under stress.