The DEAD-box helicase family member DDX3X (DBX, DDX3) functions in nearly all stages of RNA metabolism and participates in the progression of many diseases, including virus infection, inflammation, intellectual disabilities and cancer. Over two decades, many studies have gradually unveiled the role of DDX3X in tumorigenesis and tumour progression. In fact, DDX3X possesses numerous functions in cancer biology and is closely related to many well-known molecules. In this review, we describe the function of DDX3X in RNA metabolism, cellular stress response, innate immune response, metabolic stress response in pancreatic β cells and embryo development. Then, we focused on the role of DDX3X in cancer biology and systematically demonstrated its functions in various aspects of tumorigenesis and development. To provide a more intuitive understanding of the role of DDX3X in cancer, we summarized its functions and specific mechanisms in various types of cancer and presented its involvement in cancer-related signalling pathways.

FAM134B (also called JK-1, RETREG1), a member of the family with sequence similarity 134, was originally discovered as an oncogene in esophageal squamous cell carcinoma. However, its most famous function is that of an ER-phagy-regulating receptor. Over the decades, the powerful biological functions of FAM134B were gradually revealed. Overwhelming evidence indicates that its dysfunction is related to pathophysiological processes such as neuropathy, viral replication, inflammation, and cancer. This review describes the biological functions of FAM134B, focusing on its role in ER-phagy. In addition, we summarize the diseases in which it is involved and review the underlying mechanisms.