Abstract: Werner syndrome (WS) is a rare autosomal recessive genetic disease in human. It is considered as a good model disease in studying human premature syndrome. Werner protein (WRN) is a nuclear protein mutated in WS. Recent biochemical and genetic studies indicated that WRN plays important roles in DNA replication, DNA repair, and telomere maintenance. Here, we reviewed the molecular genetics of WS and the importance of telomere and WRN in the develop-ment of WS. Knocking out both telomerase and Wrn genes in mouse faithfully manifests human WS. The mouse model provides a unique genetic platform to explore the crosstalk of premature aging and tumor.