HTLV-1 has a complex genome, and contains four open reading frames (ORFs) in the 39 region encoding vi- ral and cellular regulatory proteins. p12 is a small, ORF I-encoded hydrophobic protein, the function of which is not well understood. It has been shown that p12 enhances the E5-transforming ability of bovine papillo- mavirus; and binds to the 16-kDa subunit of the vacuolar ATPase pump, immature forms of the b and gc chains of the interleukin 2 receptor, and the free chain of MHC I. p12 carrying a lysine residue (p12K) at po- sition 88 of its sequence may be rapidly degraded in the cell via proteasome, whereas p12 with an arginine residue (p12R) at the same position is severalfold more stable. These alleles are found in proviral DNA of HTLV-1-infected individuals and it was previously observed that the p12K allele was more frequent in HAM/TSP (HTLV-1-associated myelopathy/tropical spastic paraparesis) patients and was not found at all in asymptomatic carriers, whereas patients with adult T cell leukemia/lymphoma (ATLL) carry the p12R allele. To extend these observations and verify whether the p12K mutation could be used as a marker of progres- sion to HAM/TSP, we analyzed 37 HAM/TSP patients and 40 asymptomatic carriers at different stages of in- fection. In our cohort, only one HAM/TSP patient carried the p12K phenotype, which accounted for a fre- quency of 2.7% (1 of 37). We also found, among the 40 asymptomatic HTLV-1 carriers, one who presented the p12K phenotype, contrasting with previous publications. Thus, p12K does not seem to be universally di- agnostic for HTLV-1-associated neurological disease. Further screening of HTLV-1-infected individuals in other populations may elucidate this observation.