By a positional cloning/candidate gene method, Carpten et al. (2002) identified the ribonuclease L gene (180435) as the site of germline mutations in 2 HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general ... By a positional cloning/candidate gene method, Carpten et al. (2002) identified the ribonuclease L gene (180435) as the site of germline mutations in 2 HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway, and it had been a suggested tumor suppressor gene. In that connection, Carpten et al. (2002) found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozygous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway may provide opportunities for developing therapies for those with prostate cancer.