EFNA2 (ephrin A2) is a GPI-anchored cell surface ligand that binds to Eph receptor tyrosine kinases, facilitating bidirectional signaling between neighboring cells 1. The gene is located on chromosome 19.3 and encodes a protein involved in multiple physiological processes 1. EFNA2 expression is developmentally regulated, with fetal expression in brain and intestine, and adult expression primarily in lung and intestine 1. In bone metabolism, EFNA2 negatively regulates osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt signaling pathway, with upregulation contributing to osteoporosis progression 2. The protein shows sex-specific differential expression in aging skeletal muscle, being among novel genes altered in aged female muscle transcriptome 3. EFNA2 is implicated in disease pathogenesis across multiple conditions: it associates with weight loss in COPD patients, particularly among African Americans, potentially influencing skeletal muscle regeneration 4; correlates with left ventricular mass-to-volume ratio in cardiovascular disease 5; and is downregulated in lung cancer cells treated with anti-cancer compounds, with expression levels potentially affecting patient survival 6. These findings suggest EFNA2 functions as a critical regulator of tissue homeostasis, skeletal muscle biology, and disease progression.