TRIM5 is a member of a broad family of otherwise unrelated proteins defined by the presence of a tripartite motif containing a RING domain, a B-box type 1, and a B-box type 2, followed by a coiled-coil region (1). TRIM5 has five alternately spliced isoforms, the longest of which is the a variant which also contains a carboxy-terminal B30.2 (SPRY) domain (1). Expression of TRIM5a variants from humans, rhesus monkeys, and African green monkeys enabled resistance to infection by various retroviruses including HIV- 1 (2,3), albeit at differing efficiencies. The TRIM5d isoform has been shown to colocalize with the topoisomerase Iinteracting proteins BTBD1 and BTBD2 in punctate or elongated cytoplasmic bodies in several mouse and human cells where it appears to serve as a scaffold for the assembly of endogenous BTBD proteins. TRIM5 d also exhibits autoubiquitination activity in a RING finger- and UbcH5Bdependent manner (4).