The ubiquitination modification of henipavirus (HNV) M protein is essential for its nuclear-cytoplasmic trafficking and viral budding, but the precise regulatory mechanism has remained unclear. A recent study published in Emerging Microbes & Infections demonstrated that the RAD6A-RAD18 ubiquitination complex plays a unique and pivotal role in the nuclear-cytoplasmic trafficking of the HNV M protein and the process of viral budding. Furthermore, this study revealed that treating cells with TZ9 (a RAD6 inhibitor) or RAD18 RING domain-binding peptides markedly impaired the ubiquitination level of HNV M protein, resulting in its nuclear retention and subsequent impairment of viral budding and replication. These findings lay a theoretical foundation for the development of novel antiviral drugs and specific antiviral therapies targeting HNV infections, and provide valuable references for investigating the biological functions of M protein’s ubiquitination as well as the replication and pathogenic mechanisms of other paramyxoviruses.