Human T cell leukemia/lymphotropic virus types 1 and 2 are two immunologically and phylogenetically related retroviruses that differ in their pathogenicity in vivo. The overall genetic structure of HTLV-1 and -2 is similar. Each contains a unique region at the 3' end of the genome, designated the pX region. p12(I) is a membrane-associated protein encoded by the open reading frame I (ORF I) region of HTLV-1, which lies within the pX region. A corresponding protein, p10(I) is encoded by the ORF I region of HTLV-2 and an additional protein, p11(V), is encoded by ORF V, which overlaps the HTLV-2 ORF I region. As with HTLV-1, the small proteins encoded by the pX region of HTLV-2 appear to be dispensable for viral replication and cellular transformation in vitro. However, the small open reading frames of both viruses are important for viral replication in vivo, which suggests they may play an important role during the viral life cycle. This study was undertaken to investigate and compare the cellular targets of the p10(I), p11(V), and p12(I) putative proteins.