TAFA5 (TAFA chemokine-like family member 5) is a secreted protein functioning as both a chemokine-like factor and adipokine with pleiotropic roles in immune and metabolic regulation. As a chemokine-like protein, TAFA5 binds to G protein-coupled receptors, particularly S1PR2 and FPR2, to modulate cellular responses 1. In vascular tissue, TAFA5 acts as an adipokine that suppresses vascular smooth muscle cell proliferation and migration via S1PR2-G12/13-RhoA signaling, thereby inhibiting postinjury neointima formation in femoral arteries 1. TAFA5 expression is downregulated in obesity, and this reduction may contribute to cardiometabolic disease pathogenesis 1. In the nervous system, TAFA5 functions as a neurokine critical for cognitive and emotional regulation. Genetic deletion of Fam19a5 in mice increases depressive-like behaviors and impairs hippocampal spatial memory, accompanied by reduced glutamate signaling and dendritic spine density 2. Chr22 stress decreases TAFA5 levels in plasma and hippocampus, and FAM19A5 overexpression in the hippocampus attenuates stress-induced depression 2. Additionally, FAM19A5 mediates hypothalamic inflammatory responses downstream of TNF-α signaling 3. Clinically, elevated TAFA5 expression associates with poor outcomes in gastric cancer, correlating with epithelial-mesenchymal transition 3. TAFA5 variants are associated with pulmonary function in Chinese populations 4 and incident heart failure in mild obesity-related diabetes 5. TAFA5 is also implicated in major depressive disorder through OTX2-mediated gene regulation 6.