The proliferation, differentiation and homeostasis of lens anterior monolayer epithelium determine the lens growth, size, shape and transparency, which are absolutely required for focusing and transmitting a light image onto the retina. The goal of this proposal is to test a novel hypothesis that the intrinsic heterogeneity of lens epithelial cells regulates lens growth and homeostasis, and distinctive cell clusters of lens monolayer epithelium are precisely organized for mediating external signals of surrounding ocular tissues and environmental stimuli to regulate the lens growth, size, shape and transparency, and that disruptions of specific cell cluster(s) impair the regulation of lens growth and homeostasis to lead to various lens and/or eye pathological outcomes including cataracts, microphthalmia, and macrophthalmia.