N(epsilon)-(carboxymethyl)lysine, an advanced glycation end product, is present in the human lens. The effects of CML formation on protein conformation and stability were studied using the recombinant gammaC-crystallin as a model. Conformational change was studied by spectroscopic measurements such as fluorescence and circular dichroism. Conformational stability was determined by unfolding with heat. The results indicated that no conformational change was observed due to CML formation, but conformational stability decreased. These observations can be explained in terms of the relatively stable structure of gamma-crystallin, especially when compared with other crystallins. The lens nucleus is rich in gamma-crystallin and its stable conformation can assist gamma-crystallin sustained insults and remain soluble.