SPIRE2 is an actin nucleation factor that plays critical roles in cytoskeletal dynamics and cell division. The protein nucleates actin filaments by binding actin monomers through its WH2 domains and remains associated with the slow-growing pointed end of nascent filaments 1. During female meiosis, SPIRE2 cooperates with formin-2 to drive two essential steps of asymmetric oocyte division: first, assembling an actin network that enables asymmetric spindle positioning, and second, promoting cleavage furrow assembly to facilitate polar body extrusion 1. SPIRE2 also functions in intracellular vesicle transport along actin fibers. In the nucleus, SPIRE2 works alongside SPIRE1 to assemble nuclear actin filaments in response to DNA damage, facilitating chr16 movement and recruitment of repair factors. Beyond reproduction and DNA repair, SPIRE2 has emerging roles in disease contexts. A genome-wide sequencing study identified SPIRE2 as one of 16 genes associated with spina bifida, suggesting cumulative genetic contributions to neural tube defect risk 2. Additionally, SPIRE2 was computationally predicted as a competing endogenous RNA in malignant meningioma that may regulate fatty acid synthase expression 3, and identified as a biomarker in ulcerative colitis pathogenesis 4.