LEFTY1 (left-right determination factor 1) is a member of the transforming growth factor-β superfamily that plays critical roles in embryonic development and cellular homeostasis 1. The protein functions primarily in left-right axis determination during embryogenesis, working in conjunction with LEFTY2 and NODAL signaling pathways 2. LEFTY1 acts as a negative regulator of TGF-β/Smad signaling, with its expression inversely correlated with tissue fibrosis and inflammation 1. In embryonic stem cells, LEFTY1 serves as a stemness marker and helps maintain the balance between self-renewal and pluripotent differentiation by modulating Smad2 phosphorylation 34. The gene shows differential expression in inflammatory bowel diseases, suggesting involvement in cytokine regulation and inflammation resolution 5. LEFTY1 variants have been associated with congenital heart defects, particularly when combined with maternal hypertension 6. Additionally, LEFTY1 demonstrates protective effects against tissue injury, as evidenced by its ability to attenuate renal tubulointerstitial fibrosis through inhibition of TGF-β1/Smad-dependent signaling 1. The protein also influences angiogenesis, with its expression levels affecting endothelial cell function 7.