Unfolding the potential-chemical chaperones in Alport syndrome.

Chemical chaperones are small molecules that prevent protein aggregation by improving folding, relieving endoplasmic reticulum stress, and restoring secretion of misfolded proteins. Variants in COL4A3, COL4A4, and COL4A5 cause Alport syndrome, which is characterized by abnormal assembly, secretion, and incorporation of type IV collagen into basement membranes. Ioannou et al. discovered that the chaperone 4-phenylbutyric acid improved the basement membrane and kidney function in Alport mice, raising prospects for clinical translation of chaperone therapy in Alport syndrome.