The article discusses the role of RING finger proteins in mediating ubiquitin ligase activity. Initially, RING fingers were known for their role in protein dimerization, but recent studies have revealed their critical role in ubiquitination. RING fingers are found in hundreds of proteins and are involved in the transfer of ubiquitin (Ub) to both heterologous substrates and themselves. The process begins with the formation of a thiol-ester linkage between Ub and the active site cysteine of the Ub-activating enzyme (E1), followed by transfer to an Ub conjugating enzyme (Ubc or E2). E3 ligases, which provide specificity to Ub conjugation, interact with E2 and substrate to form isopeptide bonds between Ub and lysines on the target protein. RING fingers are essential for this process, facilitating the direct transfer of Ub from E2 to the substrate. The article highlights several examples of RING finger proteins, such as Rbx1, c-Cbl, and Mdm2, which play crucial roles in various cellular processes, including cell cycle regulation, apoptosis, and DNA repair. Additionally, the article discusses the regulation of RING finger E3s through phosphorylation, protein-protein interactions, and modification with Ub-like molecules like Nedd8 and SUMO-1. The discovery of numerous RING finger proteins and their potential E3 ligase activities suggests a vast array of functions in cellular processes and disease.The article discusses the role of RING finger proteins in mediating ubiquitin ligase activity. Initially, RING fingers were known for their role in protein dimerization, but recent studies have revealed their critical role in ubiquitination. RING fingers are found in hundreds of proteins and are involved in the transfer of ubiquitin (Ub) to both heterologous substrates and themselves. The process begins with the formation of a thiol-ester linkage between Ub and the active site cysteine of the Ub-activating enzyme (E1), followed by transfer to an Ub conjugating enzyme (Ubc or E2). E3 ligases, which provide specificity to Ub conjugation, interact with E2 and substrate to form isopeptide bonds between Ub and lysines on the target protein. RING fingers are essential for this process, facilitating the direct transfer of Ub from E2 to the substrate. The article highlights several examples of RING finger proteins, such as Rbx1, c-Cbl, and Mdm2, which play crucial roles in various cellular processes, including cell cycle regulation, apoptosis, and DNA repair. Additionally, the article discusses the regulation of RING finger E3s through phosphorylation, protein-protein interactions, and modification with Ub-like molecules like Nedd8 and SUMO-1. The discovery of numerous RING finger proteins and their potential E3 ligase activities suggests a vast array of functions in cellular processes and disease.