Our results indicate that HSF4 is sufficiently important to lens development and disruption of the Hsf4 gene leads to cataracts via at least three pathways: 1) down-regulation of γ-crystallin, particularly γS-crystallin; 2) decreased lens beaded filament expression; and 3) loss of post-translational modification of αA-crystallin. The gene discussed is HSF4; the disease is cataract.