Tetraspanins: Transcriptional and Post-Transcriptional Regulation and Involvement in Human Health and Diseases

Tetraspanins are a highly conserved family of transmembrane proteins that play a pivotal role in cellular signaling by forming tetraspanin-enriched microdomains (TEMs) at the plasma membrane. These microdomains interact with various signal transduction-associated proteins, thereby regulating critical processes such as cell migration, protein trafficking, and multiple signaling pathways. Dysregulation of tetraspanins at transcriptional and translational levels is implicated in several pathological conditions, including cancer. While extensive research has focused on the regulation of tetraspanins at the protein level, their transcriptional and post-transcriptional regulation remains poorly understood. This review provides a comprehensive and up-to-date synthesis of the regulatory mechanisms governed by transcription factors, epigenetic modifiers, microRNAs (miRNAs), and long noncoding RNAs on all tetraspanin family members. We have also examined the mutational landscape of tetraspanins and their pathological consequences across various diseases. Furthermore, we highlight critical gaps in current knowledge and propose future directions for research to advance our understanding of tetraspanin regulation and its therapeutic potential in disease biology.