A study identifies mutations in the TERT gene, which encodes the catalytic component of telomerase, as a cause of adult-onset idiopathic pulmonary fibrosis (IPF). The research found that mutations in TERT or TERC, the RNA component of telomerase, lead to telomere shortening, increasing susceptibility to IPF. The study analyzed two families with IPF and found mutations in TERT that cosegregated with the disease. Additional families with IPF were also analyzed, revealing more mutations in TERT. Heterozygous carriers of these mutations had shorter telomeres than age-matched family members without the mutations. The study also found that mutations in TERT or TERC can lead to telomere shortening, which may contribute to the development of IPF. The study suggests that telomere shortening is a key factor in the pathogenesis of IPF. The findings highlight the role of telomerase in maintaining telomere integrity and suggest that mutations in TERT or TERC may be a significant cause of IPF. The study also found that telomere shortening is influenced by factors such as age and the number of generations the mutation is transmitted. The study provides new insights into the molecular mechanisms underlying IPF and expands the understanding of telomerase-related diseases. The findings may lead to new therapeutic strategies for IPF by targeting telomerase activity or delaying telomere shortening.A study identifies mutations in the TERT gene, which encodes the catalytic component of telomerase, as a cause of adult-onset idiopathic pulmonary fibrosis (IPF). The research found that mutations in TERT or TERC, the RNA component of telomerase, lead to telomere shortening, increasing susceptibility to IPF. The study analyzed two families with IPF and found mutations in TERT that cosegregated with the disease. Additional families with IPF were also analyzed, revealing more mutations in TERT. Heterozygous carriers of these mutations had shorter telomeres than age-matched family members without the mutations. The study also found that mutations in TERT or TERC can lead to telomere shortening, which may contribute to the development of IPF. The study suggests that telomere shortening is a key factor in the pathogenesis of IPF. The findings highlight the role of telomerase in maintaining telomere integrity and suggest that mutations in TERT or TERC may be a significant cause of IPF. The study also found that telomere shortening is influenced by factors such as age and the number of generations the mutation is transmitted. The study provides new insights into the molecular mechanisms underlying IPF and expands the understanding of telomerase-related diseases. The findings may lead to new therapeutic strategies for IPF by targeting telomerase activity or delaying telomere shortening.