DIAPH3 is a formin family protein that nucleates and elongates actin filaments to organize the actin cytoskeleton. It binds GTP-bound Rho and recruits profilin to the membrane to promote actin polymerization in a Rho-dependent manner. Beyond cytoplasmic actin regulation, DIAPH3 also drives nuclear actin polymerization to activate serum response factor-dependent transcription. DIAPH3 is essential for cytokinesis and stress fiber formation; loss of function causes developmental defects and embryonic lethality in mice, while overexpression causes auditory neuropathy 1. Recent evidence indicates DIAPH3 specifies β-actin networks that maintain myosin II and RhoA at the cytokinetic furrow 2, and localizes at the centrosome during mitosis to regulate spindle assembly—deficiency disrupts neurogenesis and causes cortical malformation and autistic-like behavior 3. In cancer, DIAPH3 expression is regulated by the YAP transcription factor in cancer-associated fibroblasts to promote matrix remodeling and invasion 4. In hepatocellular carcinoma, alternative splicing of DIAPH3 by the lncRNA LINC01089 suppresses epithelial-mesenchymal transition 5, while in colorectal cancer, m1A-modified DIAPH3 promotes invasion by stabilizing keratin 19 6. DIAPH3 has been identified as a prognostic biomarker in glioblastoma and pancreatic cancer 78.