The E1 enzyme, also known as a ubiquitin-activating enzyme, plays a crucial role in the process of protein degradation. It is the first enzyme in the ubiquitin-proteasome pathway, which tags unwanted proteins for destruction. By activating the small protein ubiquitin, the E1 enzyme facilitates the transfer of ubiquitin to target proteins, marking them for removal. E1 enzymes are essential for maintaining cellular homeostasis by regulating protein levels and removing damaged or misfolded proteins. This process is vital for various cellular functions, including cell cycle regulation and response to stress. Dysfunction in E1 enzymes can lead to diseases, including cancer and neurodegenerative disorders.