Barrier-to-autointegration factor (BAF) is an essential protein that is highly conserved in metazoan evolution. BAF binds directly to double-stranded DNA, nuclear LEM-domain proteins, lamin A and transcription activators. BAF is also a host cell component of retroviral pre-integration complexes. BAF binds matrix, a retroviral protein, and facilitates efficient retroviral DNA integration in vitro through unknown mechanisms. New findings suggest that BAF has structural roles in nuclear assembly and chromatin organization, represses gene expression and might interlink chromatin structure, nuclear architecture and gene regulation in metazoans.