Transmembrane 4 L six family member 5 (TM4SF5)

Transmembrane 4 L six family member 5 (TM4SF5) is a tetraspanin-like transmembrane protein possessing four transmembrane domains, two extracellular loops, and short cytosolic N- and C-termini[1][2][4][6]. TM4SF5 undergoes posttranslational modifications such as N-glycosylation and palmitoylation, which enable interactions with a range of membrane proteins including growth factor receptors (e.g., EGFR, IGF1R, TGFβR), integrins (α2, α5, β1), and other tetraspanins (notably CD151)[1][2][4][5]. It organizes tetraspanin-enriched microdomains essential for spatiotemporal regulation of signal transduction involved in cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance[2][4][5]. Overexpression and pathological activation of TM4SF5 are key drivers in cancers (especially liver cancer), fibrosis, and metastatic processes[1][5]. TM4SF5 is a validated therapeutic target, with both small molecule inhibitors and antibody therapies under experimental investigation to block its pro-tumor and pro-fibrotic activities[1][2][5].

Other names

TM4SF5Transmembrane 4 superfamily member 5Tetraspan transmembrane protein L6HTransmembrane 4 L6 family member 5Tetraspanin TM4SF5

Inhibition of TM4SF5 disrupts protein interactions leading to decreased EMT, reduced cellular migration, restored contact inhibition, and inhibited tumor growth and metastasis[5]. Blockade of TM4SF5 can reverse p27kip1 cytosolic translocation, enhance RhoA activity, and reduce vascular endothelial growth factor (VEGF) expression, diminishing tumor angiogenesis[5].