The small ubiquitin-related modifier (SUMO) proteins, which include SUMO-1, SUMO-2, SUMO-3 and SUMO-4, belong to the ubiquitin-like protein family. Like ubiquitin, the SUMO proteins are synthesized as precursor proteins that undergo processing before conjugation to target proteins. Ubiquitin and SUMO proteins utilize the E1, E2 and E3 cascade enzymes for conjugation. However, SUMO and ubiquitin differ with respect to targeting. Ubiquitination predominantly targets proteins for degradation, whereas sumoylation targets proteins for a variety of cellular processing, including nuclear transport, transcriptional regulation, apoptosis and protein stability. The unconjugated SUMO-1, SUMO-2, SUMO-3 and SUMO-4 proteins localize to the nucleus. In contrast to the other SUMO proteins, SUMO-4 seems to be insensitive to sentrin-specific proteases due to the presence of Pro-90, which may impair processing to mature form and conjugation to substrates. It is suggested that defects in the gene that encodes for the SUMO-4 protein may be involved in the pathogenesis of type I diabetes.