This editorial summarizes recent advances in understanding the pathogenesis of ankylosing spondylitis (AS). Genetic studies have identified genes beyond HLA-B27 that influence AS risk, including genes involved in the IL-23 pathway and antigen processing. The association between ERAP1 and AS provides a molecular basis for the interaction between ERAP1 and HLA-B27. While early hypotheses focused on a role for CD8+ T cells, evidence now points to a central role for the IL-23/IL-17 axis, including the identification of a resident IL-23-responsive T cell population in entheseal tissues. HLA-B27 is now understood to activate the IL-23/IL-17 axis