Cataracts, which are a major cause of blindness, result when one or more of the structural crystallins aggregate, causing opacity of the lens. This appears to occur after the alpha-crystallins have been titrated out. The crystal structures of normal human gammaD crystallin and a less soluble mutant form implicated in cataracts have been solved. Branched, filamentous aggregates of this protein have been observed in vitro, but details of their molecular structure are not known. Dye-binding assays suggest that the structure of the fibrillar aggregates found in cataracts may be similar to amyloid fibrils, although interesting differences seem likely because amyloid fibrils are typically unbranched. Solid-state NMR methods that have been previously applied to other locally-ordered systems, such as amyloid fibrils and silk will allow comparisons between the structure of this aggregate and the crystal structure of the native protein. Discovering the differences between these two forms of gammaD crystallin may help in understanding the process of cataract formation. Future studies to be performed on this system will include investigations of the native state of the eye lens. Although the complexes between alpha- and beta/gamma-crystallins are far too large for solution-state NMR (up to 1 MDa), the individual protein monomers are small, and the complexes have significant short-range order. This should enable their investigation by solid-state NMR. This structural study of the native and cataract forms of the eye lens crystallins is representative of the long-term goals of the Martin laboratory.