Protein folding is the most error-prone step in gene expression and contributes to all degenerative diseases including neurodegeneration, metabolic syndrome, inflammation and cancer. Protein misfolding causes protein aggregation that causes cell death. Unfortunately there is a dearth of information regarding how protein aggregation is controlled in the cell. In a report published in Mol. Biol. Cell, Dr. Kaufman’s lab describes how protein solubility in the endoplasmic reticulum requires a unique enzyme UGGT1, a gene that was first isolated by Dr. Kaufman years ago. Now the Kaufman lab has demonstrated that this enzyme controls the aggregation of different mutant forms of the protein a-1-antitrypsin(a1-AT), which is produced in the liver. One mutation in (a1-AT), the Z-allele, is the most common cause of liver failure in children. Kaufman’s studies demonstrate that UGGT1 promotes protein solubility of (a1-AT-Z) and protects cells from death. The findings provide novel insight into potential avenues to treat and/or prevent the most common devastating liver disease in children.