High mobility group 1 (HMG1) is a 26 kDa highly conserved non-sequence-specific DNA binding nuclear protein. Mammalian HMG1 has two homologous DNA binding domains HMG boxes, A and B (each of 80 90 aminoacid residues), linked by a short basic region to an acidic C terminal domain containing 30 consecutive Asp and Glu residues. HMG1 has been implicated in a number of fundamental biological processes including transcription, replication and recombination, in which it plays a role in manipulating DNA structure by bending, looping, compaction or unwinding, or by direct contacts with distinct cellular proteins. HMG1 can act as a repressor, by interacting with TBP to block pre initiation complex formation or as an activator, by facilitating the binding of various transcription factors to their cognate DNA sequences. Most recently, it was discovered that HMG1 is a late mediator of delayed endotoxin lethality by activating downstream cytokine release.