Although these investigations from multiple laboratories have proven to be very informative for gaining insight to WRN’s roles in maintenance of genomic stability mediated by its functions at telomeres, stalled forks, and key DNA recombination intermediates, the enzyme is still enigmatic in terms of establishing direct relationships between its molecular functions and cellular pathways critical for genome homeostasis and suppression of gerontological phenotypes characteristic of the accelerated aging disorder WS. This evidence concerns the gene WRN and Werner syndrome.