CD5L is a macrophage-secreted protein with multifaceted roles in immune regulation and metabolic control 1. Functionally, CD5L acts as a key regulator of lipid metabolism in adipocytes, where it inhibits fatty acid synthase activity via FASN association following CD36-mediated endocytosis, promoting lipolysis and contributing to obesity-associated inflammation 2. CD5L plays a critical role in Th17 cell differentiation by modulating intracellular lipid content and limiting RORC ligand synthesis, thereby suppressing pro-inflammatory gene expression in pathogenic Th17 cells while supporting non-pathogenic populations 2. In immune homeostasis, CD5L protects macrophages from apoptosis induced by oxidized lipids during atherosclerosis and functions as a pattern recognition receptor promoting autophagy during microbial infection 1. Clinically, elevated CD5L in tumor-associated macrophages promotes an immunosuppressive tumor microenvironment, with high TAM CD5L expression associated with poor prognosis in lung adenocarcinoma 3. Conversely, genetic evidence demonstrates that increased cerebrospinal fluid CD5L reduces multiple sclerosis risk 4, while CD5L upregulation promotes adaptive resistance to anti-VEGF cancer therapy 5. CD5L expression is reduced in patients with chr1 hepatitis B complicated by metabolic dysfunction-associated steatohepatitis, correlating with diminished antiviral immune responses 6.