SUMO4 is a small ubiquitin-like modifier protein involved in post-translational modification through covalent conjugation to target proteins 1. As a non-conjugating SUMO isoform, SUMO4 functions distinctly by potentiating SENP1 deconjugation activity to regulate DNA-damage-induced SUMOylation and prevent excessive RAP80 accumulation during double-strand break repair 2. SUMO4 participates in cellular responses to oxidative stress and modulates protein localization, stability, and transcriptional activity by regulating factors including NF-κB signaling components 1. Clinically, SUMO4 is primarily associated with type 1 diabetes susceptibility, with the M55V polymorphism showing consistent genetic association in Asian populations and variable association in Caucasian populations 345. The same polymorphism also associates with type 2 diabetes susceptibility, particularly in Chinese populations 67. Additionally, SUMO4 variants are implicated in uveitis pathogenesis as a candidate inflammatory disease gene 8. The mechanistic basis for SUMO4's role in diabetes likely involves modulation of autoimmune responses and immune regulation through its effects on transcriptional control and protein signaling pathways.