Crystallins are the predominant structural proteins in the lens that are evolutionarily related to stress proteins. They were first discovered outside the vertebrate eye lens by Bhat and colleagues in 1989 who found αB-crystallin expression in the retina, heart, skeletal muscles, skin, brain and other tissues. With the advent of microarray and proteome analysis, there is a clearer demonstration that crystallins are prominent proteins both in the normal retina and in retinal pathologies, emphasizing the importance of understanding crystallin functions outside of the lens. There are two main crystallin gene families: α-crystallins, and βγ-crystallins. α-crystallins are molecular chaperones that prevent aberrant protein interactions. The chaperone properties of α-crystallin are thought to allow the lens to tolerate aging-induced deterioration of the lens proteins without showing signs of cataracts until older age. α-crystallins not only possess chaperone-like activity in vitro, but can also remodel and protect the cytoskeleton, inhibit apoptosis, and enhance the resistance of cells to stress. Recent advances in the field of structure-function relationships of α-crystallins have provided the first clues to their underlying roles in tissues outside the lens. Proteins of the βγ-crystallin family have been suggested to affect lens development, and are also expressed in tissues outside the lens. The goal of this paper is to highlight recent work with lens epithelial cells from αA- and αB-crystallin knockout mice. The use of lens epithelial cells suggests that crystallins have important cellular functions in the lens epithelium and not just the lens fiber cells as previously thought. These studies may be directly relevant to understanding the general cellular functions of crystallins.