SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis

This study investigates how loss of the ER transporter SLC33A1 affects glutathione redox balance and protein cysteine reactivity in the endoplasmic reticulum. Oxidized cysteine reactivity profiling and whole-cell proteomics were performed in Slc33a1 knockout KPK cells and cDNA-complemented controls. Quantitative TMT-based proteomics identified increased oxidation of protein disulfide isomerases and other ER-resident proteins, indicating disruption of ER redox homeostasis and proteostasis. Additional experiments examined unfolded protein response activation and genetic interactions with ER quality-control pathways. The dataset includes cysteine reactivity profiling and unenriched proteomics data acquired by LC–MS/MS and processed using standard proteomics pipelines.