TNF-α–induced protein 8–like 2 (TIPE2 or TNFAIP8L2) is a recently discovered negative regulator of innate and adaptive immunity. TIPE2 is expressed in a wide range of tissues, both immune and nonimmune, and is implicated in the maintenance of immune homeostasis within the immune system. Furthermore, TIPE2 has been shown to play a pivotal role in the regulation of inflammation and the development of tumor. This review focuses on the structural characteristics, expression patterns, and functional roles of TIPE proteins, with a particular emphasis on the role and underlying mechanisms of TIPE2 in immune regulation and its involvement in different diseases. However, the current body of evidence is still limited in providing a comprehensive understanding of the complex role of TIPE2 in the human body, warranting further investigation to elucidate the possible mechanisms and functions of TIPE2 in diverse disease contexts.

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