Knock-in mice provide useful models of congenital and age-related cataracts caused by α-crystallin mutations.

R49C αA-crystallin and R120G αB-crystallin mutations are linked with hereditary cataracts.

Mutant crystallin cannot function as a chaperone, which leads to protein aggregation and lens opacity.

Mutated crystallins alter lens morphology, autophagy, and stress responses.

Therapeutic modulation of autophagic pathways may improve protein degradation in cataractous lenses and reduce lens opacity.