FES encodes a cytoplasmic tyrosine kinase that plays protective roles in cardiovascular and cellular homeostasis. The protein functions downstream of cell surface receptors to regulate actin cytoskeleton organization, microtubule assembly, cell attachment, and migration 1. FES acts in FCER1-mediated signaling in mast cells and promotes neurite outgrowth in response to NGF signaling. Mechanistically, FES phosphorylates multiple substrates including BCR, HCLS1/HS1, PECAM1, STAT3, and TRIM28, with its kinase activity being tightly regulated in vivo to prevent oncogenic transformation 2. Clinically, genetic variants at the 15q26.1 locus reduce FES expression in monocytes, contributing to increased coronary artery disease susceptibility 1. FES depletion promotes monocyte and vascular smooth muscle cell migration, leading to larger atherosclerotic plaques with increased inflammatory cell content in mouse models 1. The protein's protective role against atherosclerosis suggests that enhancing FES activity could represent a novel therapeutic approach for coronary artery disease intervention. Despite its proto-oncogene classification, overexpressed wild-type FES remains non-transforming due to cellular regulatory mechanisms that restrain its kinase activity 2.