The role of α-crystallin as a molecular chaperone may explain how the lens stays transparent for so long. α-Crystallin prevents the aggregation of other lens crystallins and proteins that have become unfolded by “trapping” the protein in a high molecular weight complex. It also protects enzyme activities. The substrate protein may interact while in a molten globule state. α-Crystallin predominantly binds to proteins very early in the denaturation pathways. The amphiphilic nature of α-crystallin, a polar C-terminal-region and a hydrophobic N-terminal-region are all essential for chaperone function. The flexible C-terminal extension maintains solubility and can bind to opposing charged residues of unfolding proteins. Hydrophobic regions in the N-terminal region then hold the unfolded protein. Specific areas important for chaperone binding and function have been identified throughout the N-terminal-region, connecting peptide and C-terminal extension. After a substantial amount of chemical data and models, cryo-EM images of α-crystallin have confirmed a variable 3D surface with a hollow interior. α-Crystallin taken from the lens nucleus shows an age-dependent decrease in chaperone function. High molecular weight aggregates and α-crystallin found within the nucleus from clear and cataract lenses have reduced chaperone function. Post-translational modifications, known to occur during ageing, such as glycation, carbamylation, oxidation, phosphorylation and truncation cause a decrease in chaperone function. α-Crystallin is expressed outside the lens. αB-Crystallin can be induced by heat shock in many tissues where it is translocated from cytoplasm to nucleus. Increased expression of αB-crystallin has been seen in many pathological states. Conformational disorders, including cataract may have a common aetiology and potentially a common therapy.