This study investigates the genetic basis of adult-onset pulmonary fibrosis (IPF), a lethal scarring lung disease of unknown etiology. Using linkage analysis, researchers identified a disease gene on chromosome 5, which was found to contain mutations in the TERT gene, encoding telomerase reverse transcriptase. These mutations, including a frameshift mutation and multiple missense mutations, were associated with shorter telomeres and increased susceptibility to IPF. Additionally, a heterozygous mutation in TERC, the RNA component of telomerase, was identified in one family. The study suggests that mutations in TERT or TERC leading to telomere shortening significantly increase the risk of developing IPF. The findings provide new insights into the pathogenesis of IPF and highlight the potential therapeutic targets for this disease.This study investigates the genetic basis of adult-onset pulmonary fibrosis (IPF), a lethal scarring lung disease of unknown etiology. Using linkage analysis, researchers identified a disease gene on chromosome 5, which was found to contain mutations in the TERT gene, encoding telomerase reverse transcriptase. These mutations, including a frameshift mutation and multiple missense mutations, were associated with shorter telomeres and increased susceptibility to IPF. Additionally, a heterozygous mutation in TERC, the RNA component of telomerase, was identified in one family. The study suggests that mutations in TERT or TERC leading to telomere shortening significantly increase the risk of developing IPF. The findings provide new insights into the pathogenesis of IPF and highlight the potential therapeutic targets for this disease.