Abstract: Ubiquitin-specific protease 15 (USP15), a member of the deubiquitinating enzyme family, belongs to cysteine protease. Recent studies have revealed that USP15 can mediate the regulation of stability and function of various cellular proteins directly or indirectly, and exert an influence on the occurrence and development of tumor and many other diseases. Therefore, USP15 may become a potential molecular target for treating related diseases. This article summarized the recent research progresses of USP15 on its gene localization and expression and relationship with related diseases.