JAML (junction adhesion molecule like) is a transmembrane glycoprotein that plays diverse roles in immune cell activation, disease pathogenesis, and cancer progression. The protein facilitates γδ T-cell activation through interaction with CXADR on epithelial cells, promoting downstream signaling via PI3-kinase and MAP kinases 1. JAML demonstrates tissue-specific expression patterns, being highly expressed in tissue-resident memory CD8+ T cells where it provides costimulatory signals for antitumor immunity 23. However, JAML exhibits context-dependent functions across different disease states. In diabetic kidney disease, elevated JAML expression in podocytes promotes lipid accumulation through SIRT1-mediated SREBP1 signaling, contributing to disease progression 14. In atherosclerosis, macrophage-expressed JAML promotes inflammation by activating the NF-κB pathway and NLRP3 inflammasome through PKM2 nuclear translocation 5. JAML also demonstrates oncogenic properties in lung adenocarcinoma by promoting tumor progression via Wnt/β-catenin signaling and PI3K/AKT/mTOR pathways 67. This dual nature positions JAML as both a potential therapeutic target for inflammatory diseases and metabolic disorders, and as a promising immunotherapy target for cancer treatment 8.