TLE6 encodes a core component of the subcortical maternal complex (SCMC), a multiprotein complex essential for early mammalian embryonic development 1. The SCMC consists of TLE6, NLRP5 (MATER), and OOEP (FLOPED), with TLE6 being embraced by MATER through its NACHT and LRR domains 1. Functionally, the SCMC regulates cell cycle progression during maternal-to-embryo transition by stabilizing 14-3-3 protein and controlling CDC25B, thereby ensuring proper activation of maturation-promoting factor and mitotic entry in zygotes 2. TLE6 recruitment to the SCMC is enhanced by phosphorylation 2. Mutations in TLE6 cause oocyte/zygote/embryo maturation arrest 15, a reproductive disorder characterized by preimplantation embryonic developmental arrest 34. Pathogenic TLE6 variants can result in aberrant RNA splicing and protein truncation, leading to disrupted maternal mRNA clearance and failure of embryo genome activation 4. The structural basis of human SCMC reveals that missense variants like p.A396T can destabilize the complex, providing a mechanism-based approach for identifying deleterious variants associated with female infertility 5. TLE6 deficiencies are among the genetic causes of total fertilization failure and recurrent IVF/ICSI failure, highlighting its clinical significance in reproductive medicine 67.