Human endogenous retroviruses (HERVs) are repetitive elements that are derived from ancient germline retroviral infections. Due to their ability to move and insert next to certain genes and alter expression patterns, HERVs have been linked to several chronic diseases such as nervous systemic diseases, cancer, autoimmune and connective tissue diseases. The HERV-H family is the most abundant HERV family and has been implicated in the expression of a variety of adjacent genes. Proteins belonging to the HERV-H family are divided into one major and two minor groups based on sequence divergence. As a member of the HERV-H family, HHLA2 (HERV-H LTR-associating protein 2) is a 414 amino acid single-pass type I membrane protein that contains one Ig-like C1-type (immunoglobulin-like) domain and two Ig-like V-type (immunoglobulin-like) domains. HHLA2 is primarily expressed in kidney, lung and intestinal tissues.