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Ankylosing spondylitis (AS) is a highly heritable kind of arthritis that affects the vertebral column. AS risk has been associated strongly with Human leukocyte antigen (HLA)-B*27. In fact, some HLA-B*27 subtypes have been associated with the increased disease risk, although some specific subtypes have not shown such associations. It is supposed that HLA-B*27 plays a major role in the etiopathogenesis of the disease. However, the difference in pathogenic outcomes of HLA-B*27 certain subtypes needs to be clarified. The purpose of this review article is to overview on the detailed implications of the HLA-B*27 subtypes in the etiopathogenesis of AS. Moreover, the role of ERAP1 in AS and its epistasis with HLA-B*27 have been reviewed.