DIAPH2 (diaphanous related formin 2) is a formin family protein that regulates actin cytoskeletal dynamics and endosome function. As an FDD-type formin homology protein, DIAPH2 contains FH1 and FH2 domains that facilitate actin filament polymerization and interact with regulatory proteins including Profilin. 1 The protein participates in a RhoA-dependent signaling pathway regulating endosome motility through actin-cytoskeleton interactions. 2 Clinically, DIAPH2 mutations are associated with primary ovarian insufficiency (POI), a condition characterized by follicle exhaustion leading to infertility before age 40. 3 The gene is implicated in ovarian development and meiosis pathways essential for female gamete generation. 3 Additionally, DIAPH2 expression in developing cochlear stereocilia suggests a potential role in inner ear function, though knockout studies have not yet demonstrated conclusive hearing loss. 2 Genetic polymorphisms in DIAPH2, particularly rs6620138 and rs12851931, have been associated with laryngeal squamous cell carcinoma susceptibility in men, with certain variants linked to higher tumor stages and smoking exposure. 45 DIAPH2 mutations represent one of seven formin genes identified as causing various inherited human disorders. 6