Diverse Roles of Tubulin Polymerization Promoting Protein 3 (TPPP3) in Human Health and Disease

The tubulin polymerization promoting proteins (TPPPs) are a small family of conserved proteins originally characterized as microtubule binding proteins. TPPP1, the first identified member, both binds to and bundles microtubules. Its homologs, TPPP2 and TPPP3, are encoded by separate genes on distinct chromosomes but both lack the N-terminal tail present in TPPP1. Functional studies revealed that TPPP3 retains comparable microtubule binding and bundling capacity to TPPP1, whereas TPPP2 displays markedly reduced binding and no bundling activity. Intriguingly, TPPP3 has been implicated in many different diseases. In this review, we summarize the current findings on TPPP3 and its dysregulation in various diseases including cancer, reproductive dysfunction, musculoskeletal conditions, endothelial dysfunction, and neurodegenerative diseases.