Abstract: α-crystallins are an important member of the small-molecule heat shock protein family (sHSP), including αA-crystallin and αB-crystallin, which have cytoprotection and molecular chaperone functions in various cells and tissues. In recent years, it has been found that retinal α-crystallins are involved in proliferative retinal diseases via regulating angiogenesis and epithelial/endothelial-mesenchymal transition. This article introduces the specific mechanism of α-crystallins, especially αB-crystallin, in regulating the development of proliferative retinal diseases, and its potential clinical application.