AMIGO3 is a type I transmembrane adhesion molecule with an immunoglobulin-like domain that mediates heterophilic cell-cell interactions and contributes to signal transduction through its intracellular domain 1. In the central nervous system, AMIGO3 functions as a component of the Nogo-66 tripartite receptor complex alongside LINGO-1 and p75NTR/TROY, substituting for LINGO-1 to signal axon growth cone collapse through the RhoA pathway following CNS injury 2. Suppression of AMIGO3 expression promotes neurotrophin-3-mediated regeneration of dorsal column axons in spinal cord injury models, with AMIGO3 knockdown enabling functional recovery of sensory and locomotor function 2. Beyond its neurobiological role, AMIGO3 has emerged as a prognostic marker in cancer biology. Differential methylation of AMIGO3 is significantly associated with prostate cancer progression in African American cohorts 3, and AMIGO3 was identified as one of twenty independent immune-related risk factors for colorectal cancer survival, contributing to machine learning-based prognostic models with concordance indices of 0.852-0.818 for 1-5 year survival prediction 4. These findings establish AMIGO3 as a multifunctional adhesion molecule with roles in axonal regeneration and cancer prognosis.