Tissues of the eye depend on closely regulated developmental pathways and families of specialized proteins. These include the crystallins of the lens. We have shown that in humans and other species, crystallins have arisen by a process called Gene Recruitment. The origins and functions of many classes of crystallins have been elucidated. gS-crystallin is the major bg-crystallin in the adult human lens. Ablation of the gene for gS leads to disruption of normal fiber cell organization and processing of cell nuclei. In particular, the actin cytoskeleton and cell junctions are aberrant, and protein complexes ?crystallize? in the cell membrane. This suggests a key functional role for gS in structural organization in normal lens development. We have discovered a new member of the g-crystallin family, gN, which has a gene structure that combines features of both b- and g- gene families and is expressed in lens, photoreceptors and RPE in mouse. gN gene and cDNAs have been identified in several species and this family seems to be an intermediate in the evolution of the bg superfamily. EST analyses have characterized complete families of crystallins in several species, particularly zebrafish. This has revealed conserved members of gS, gN and gM families and a novel, third member of the alpha-crystallin family. Structure function studies are in progress. g-Crystallins are often associated with cataract. We have found that the No3 cataract in mice is caused by insertion of an endogenous retrovirus into the gene for gE-crystallin, giving rise to an aberrant protein. It also points to a source of active ERV in the mouse genome