TM9SF2 is a transmembrane protein belonging to the conserved TM9SF family, characterized by nine putative transmembrane domains and a variable extracellular domain 1. The protein localizes to the plasma membrane and cytoplasm in most cell types, though its expression is preferentially elevated in lung tissue 1. TM9SF2 functions as a channel or small molecule transporter in intracellular compartments, with demonstrated roles in Golgi integrity and cholesterol trafficking 2. Mechanistically, TM9SF2 maintains proper Golgi apparatus organization and facilitates retrograde transport pathways critical for ricin-induced cytotoxicity 2. The protein is essential for AAV transduction across multiple serotypes, mediating post-internalization intracellular trafficking events 3. In disease contexts, TM9SF2 is implicated as a colorectal cancer oncogene, with elevated expression in approximately 35% of CRC patients correlating with poor prognosis and disease progression 4. TM9SF2 knockdown reduces cancer cell growth and fitness through alterations in cell cycle progression and ceramide signaling 4. Additionally, TM9SF2 upregulation is associated with osteoarthritis severity through enhanced M2 macrophage phagocytosis 5, and serves as a shared biomarker between ischemic stroke and obstructive sleep apnea with negative correlation to monocyte infiltration 6.