AMER2 (APC membrane recruitment protein 2) is a vertebrate-specific negative regulator of canonical Wnt/β-catenin signaling with dual roles in signal transduction and cytoskeletal dynamics 1. AMER2 functions by binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) via lysine-rich motifs, enabling membrane translocation where it recruits APC and links the β-catenin destruction complex (containing axin and conductin) to the plasma membrane 1. This membrane localization is essential for suppressing Wnt target gene expression 1. Beyond canonical Wnt inhibition, AMER2 interacts with the microtubule plus-end tracking protein EB1 through specific (S/T)xIP motifs, stabilizing microtubules at the plasma membrane and promoting cell migration 2. AMER2 represents one member of a vertebrate-specific gene family (AMER1/WTX, AMER2, AMER3) that arose through whole-genome duplications 3, with AMER2 and AMER1 functioning as Wnt pathway inhibitors while AMER3 acts as an activator 4. In Xenopus embryos, AMER2 is primarily expressed in dorsal neuroectoderm and neural tissues, where its knockdown disrupts neuroectodermal patterning through increased Wnt signaling 1. Clinically, AMER2 DNA methylation patterns correlate with gastric carcinoma aggressiveness and patient prognosis 5, and methylation changes occur progressively during colorectal cancer development 6.