The role of E3 ubiquitin ligases in vertebrate eye development: Mechanisms and emerging perspectives.

The vertebrate eye is a highly specialized and evolutionarily conserved organ whose development involves a complex interplay of signaling pathways, transcriptional regulation, and post-translational protein modifications. Among these, the ubiquitin-proteasome system (UPS) has emerged as a crucial regulatory axis for maintaining protein homeostasis during ocular organogenesis. E3 ubiquitin ligases, as key specificity-determining components of the UPS, mediate the selective ubiquitination and subsequent degradation or functional modulation of a wide array of target proteins involved in cell fate determination, proliferation, differentiation, and apoptosis. In recent years, accumulating evidence has revealed that various classes of E3 ligases-including RING-type, HECT-type, and Cullin-RING ligases-play indispensable roles in the development of multiple ocular structures, such as the retina, lens, and optic cup. This review systematically summarizes the current understanding of E3 ligase-mediated regulatory mechanisms in vertebrate eye development, with particular emphasis on their substrates, signaling pathways, and functional consequences. We also discuss the involvement of E3 ligase dysregulation in congenital ocular disorders and highlight emerging technologies, such as CRISPR-based screening and targeted protein degradation tools, which offer new opportunities for dissecting E3-substrate networks and therapeutic modulation. This comprehensive overview aims to provide mechanistic insights and future perspectives into the role of E3 ubiquitin ligases in eye development and disease.