SLC33A1 (solute carrier family 33 member 1) functions as an acetyl-CoA transporter that mediates active transport of acetyl-CoA across the endoplasmic reticulum (ER) membrane into the ER lumen 1. This transported acetyl-CoA serves as substrate for ER-based acetyltransferases that modify various molecules, including sialic acid residues of gangliosides and lysine residues of membrane proteins 1. Recent findings reveal SLC33A1 also functions as the major ER oxidized glutathione (GSSG) exporter, maintaining ER redox homeostasis by preventing GSSG accumulation and ensuring proper protein disulfide formation 2. The protein is ubiquitously expressed and phylogenetically conserved, suggesting fundamental importance 1. Disease associations include spastic paraplegia 42 (SPG42), where mutations like p.Ser113Arg act in a dominant-negative manner and dysregulate BMP signaling 3. SLC33A1 shows context-dependent roles in cancer: it represents a specific dependency in KEAP1-mutant lung adenocarcinomas 4, while low expression correlates with poor prognosis in ovarian cancer 5. The gene is also implicated in hepatocellular carcinoma as a potential therapeutic target 6. Loss of SLC33A1 function leads to ER stress and increased dependency on ER-associated degradation pathways 2.