Sumo is a highly conserved, approximately 90 amino acid ubiquitin-like protein that is conjugated to substrates through a cascade of E1 activating enzymes, E2 conjugating enzymes, and E3 ligases. Conjugation of Sumo to target proteins (sumoylation) regulates their activity, stability, subcellular localization, or macromolecular interactions. Sumoylation is reversible and is used to regulate many processes with central roles in development including signal transduction, the epigenetic control of transcription, and the development and function of the innate immune system. (Adapted from PMID:28234446 and PMID:32188601.)