DIAPH3 is a formin family actin nucleator and elongation factor that nucleates F-actin structures including stress fibers and actin cables 1. The protein contains functional FDD, FH1, and FH2 domains characteristic of formin-homology proteins, with the FH1 domain binding profilin and the FH2 domain modifying actin filaments 1. DIAPH3 functions as a Rho-dependent effector, binding GTP-bound Rho to recruit profilin to the membrane and promote actin polymerization [UniProt]. The protein performs dual cytoplasmic and nuclear roles: cytoplasmically, it regulates stress fiber formation and cytokinesis by nucleating β-actin networks essential for maintaining myosin-II and RhoA at the cytokinetic furrow 2; nuclearly, it drives serum-dependent SRF-MRTFA activity through nuclear actin polymerization. DIAPH3 activity is tightly regulated through DID-DAD autoinhibitory domain interactions that are disrupted by RhoA binding, with Stub1-mediated ubiquitination of activated DIAPH3 providing negative feedback 3. Disease associations include autosomal dominant auditory neuropathy, where DIAPH3 overexpression causes pathology 3. DIAPH3 is dysregulated in multiple cancers: in hepatocellular carcinoma, alternative splicing of DIAPH3 exon 3 driven by the lncRNA LINC01089 suppresses tumor suppressive functions and promotes EMT 4; in breast cancer, YAP-regulated DIAPH3 contributes to cancer-associated fibroblast activation and matrix remodeling 5; and in pancreatic cancer and glioblastoma, DIAPH3 serves as a prognostic biomarker linked to malignant cell proliferation 67.