c-Jun activation domain-binding protein 1 (JAB1) was originally identified as a c-Jun co-activator and subsequently discovered to be a component of the COP9 signalosome (CSN) complex. JAB1, which is also known as CSN5, affects many partner proteins through protein-protein interaction, which leads to protein degradation and transcriptional activation. Thereby, JAB1/CSN5 functions as a multifunctional protein involved in the regulation of cell cycle, signal transduction, and DNA repair. In particular, JAB1/CSN5 plays an essential role in tumorigenesis by degrading tumor suppressor proteins and activating oncogenic transcription factors. JAB1/CSN5 overexpression has been observed in various types of cancer, and it has been multifunctionally involved in cancer progression.