E1 enzymes, also known as ubiquitin-activating enzymes, play a crucial role in the ubiquitin-proteasome system. They are responsible for activating ubiquitin, a small protein that tags other proteins for degradation. This process is essential for regulating various cellular functions, including protein turnover and response to stress. These enzymes work by forming a high-energy thioester bond with ubiquitin, which is then transferred to E2 enzymes, or ubiquitin-conjugating enzymes. The E1 enzyme is the first step in a cascade that ultimately leads to the attachment of ubiquitin to target proteins, marking them for destruction by the proteasome.