SUMO1 is a small ubiquitin-like modifier that functions as a post-translational protein modification regulating diverse cellular processes including nuclear transport, DNA replication and repair, mitosis, and signal transduction 1. SUMO1 is covalently attached to target proteins through an enzymatic cascade involving E1 (SAE1-SAE2), E2 (UBE2I), and E3 ligases 1. The protein plays paralog-specific roles distinct from SUMO2/3, sharing only 47% sequence homology while SUMO2/3 share 97% homology with each other 1. SUMO1-modified protein substrates include the potassium channel KCNB1, where modification modulates gating characteristics 1, and Drp1, where SUMO1ylation promotes mitochondrial fission 23. In pathophysiology, SUMO1 dysregulation contributes to intervertebral disc degeneration through MAPL-mediated Drp1 SUMOylation and excessive mitochondrial fission 3, while SUMO1 hypersumoylation supports glioma stem cell maintenance 4. SUMO1-derived peptides show therapeutic potential in Parkinson's disease by inhibiting α-synuclein aggregation 5. Small-molecule SUMO1 degraders demonstrate anticancer efficacy by promoting ubiquitin ligase-mediated SUMO1 degradation in patient-derived tumors 6. Non-syndromic orofacial cleft 10 represents a known disease association, suggesting roles in palatal development.