Epstein–Barr virus‐induced molecule 2 (EBI2) is well known as a chemotactic receptor for B cells, T cells, dendritic cells (DCs) and other various cell populations. With the deepening of research, it is thought that EBI2 may also play a key role in functional responses, such as immune regulation, differentiation and tissue homeostasis. An abnormal expression of EBI2 has been considered to be associated with diseases, including inflammation and chronic diseases. In this review, we expounded the molecular mechanism of activation of EBI2 stimulated by its most effective agonist, 7α, 25‐OHC, and discussed typical research findings on EBI2 in immune control in recent decades. In addition, diseases caused by unusual EBI2 regulation have also been discussed, especially chronic obstructive pulmonary disease (COPD). In conclusion, EBI2 has been potentially regarded as a therapeutic target for chronic inflammation.