MAPRE2 encodes EB2 (microtubule end-binding protein 2), a critical regulator of microtubule dynamics and cellular organization. The protein stabilizes microtubules and anchors them at centrosomes, ensuring proper mitotic progression and genome stability 1. MAPRE2 plays essential roles in cell migration by regulating focal adhesion dynamics and recruiting HAX1 to microtubules 2. In cardiac physiology, MAPRE2 modulates voltage-gated sodium channel function through microtubule-related trafficking effects on NaV1.5 expression, with knockout models showing decreased conduction velocity and sodium current density characteristic of Brugada syndrome 34. During development, MAPRE2 is crucial for cranial neural crest cell migration, with mutations disrupting focal adhesions and causing craniofacial malformations in CSC-KT syndrome 5. Loss-of-function mutations in MAPRE2 cause congenital symmetric circumferential skin creases type 2 (CSCSC2), characterized by intellectual disability, growth delay, and distinctive skin creases 67. The protein also contributes to cancer progression, with upregulation promoting pancreatic cancer cell invasion and ESCC proliferation through enhanced angiogenesis 89. These diverse functions highlight MAPRE2's fundamental role in microtubule organization across multiple biological processes.