SAE1 (SUMO1 activating enzyme subunit 1) functions as a critical component of the SUMOylation machinery, forming a heterodimer that acts as an E1 ligase for SUMO proteins 1. The SAE1-containing complex mediates ATP-dependent activation of SUMO1, SUMO2, and SUMO3, leading to formation of thioester bonds between SUMO proteins and target substrates 1. This post-translational modification regulates protein stability, trafficking, protein-protein interactions, and cellular activity rather than protein degradation 1. SAE1 has emerged as a significant oncogenic driver across multiple cancer types, with overexpression associated with poor prognosis in gastric cancer 2, hepatocellular carcinoma 3, pancreatic adenocarcinoma 4, and breast cancer 5. In hepatocellular carcinoma, SAE1 interacts with YY1 transcription factor to promote Wnt pathway activation and cellular invasion 3. SAE1 also plays a role in therapy resistance, as hyperactive SUMO signaling contributes to proteasome inhibitor resistance in multiple myeloma 6. Clinically, SAE1 represents a potential therapeutic target, as inhibition through compounds like ginkgolic acid can induce ferroptosis and reduce fibrosis 7, while SUMO pathway inhibitors show promise in overcoming drug resistance 6.