SPARC (secreted protein acidic and rich in cysteine)- null mice all began to develop cataract at an early age indicates that the SPARC gene is critical to lens functions and transparency. Although cataract is the primary cause of blindness worldwide, the importance of lens epithelial cells in regulation of cataractogenesis is not fully understood. This proposal outlines 2 specific aims attempting to understand the role of SPARC in lens epithelial cell proliferation and differentiation. The lens is derived from one cell type (lens epithelium). Lens epithelial cells proliferate and differentiate into fiber cells that constitute the body of the lens throughout life. This process is regulated tightly by environmental cues and is critical for normal lens growth. SPARC, a secreted prototypic matricellular glycoprotein with counteradhesive and antiproliferative functions, might be a key factor in the regulation of this process. SPARC-null mice provide an excellent opportunity for understanding not only cataractogenesis but also the function(s) of SPARC itself.