WD40 repeat (WDR) domain is one of the most abundant protein interaction domains in the human proteome. More than 360 protein interaction domains have been annotated until now. WDR domains frequently mediate interaction with peptide regions of important interaction partners during a variety of biological processes. Proteins with WDR domain which is typically a seven-bladed β propeller, are continuously being discovered. They represent a large class of proteins that are likely to be central proteins. WDR domain-containing protein 76 (WDR76) is a member of WDR domain-containing protein. It is still poorly understood with possible involvement in DNA damage repair, apoptosis, cell cycle progression, and gene expression regulation. With further study on WDR76, knowledge of its basic functions and its role in different pathophysiological processes are increasing. Diverse interactions between WDR76 and its partners are complex and made a study on WDR76 challenging. In the present review, we summarized the process of understanding WDR76, its physiological functions, the close relationship with human diseases, and further potential opportunity for target therapy.