TGFBR3 (transforming growth factor beta receptor 3) is a non-kinase co-receptor in the TGF-β signaling pathway that lacks serine/threonine kinase activity 1, distinguishing it from TGFBR1 and TGFBR2. As a co-receptor, TGFBR3 acts as a TGF-β2-specific receptor that facilitates SMAD2 phosphorylation and downstream signaling 2. TGFBR3 functions to regulate cell migration, angiogenesis, and epithelial-mesenchymal transition through modulation of TGF-β superfamily pathways 1. Clinically, TGFBR3 demonstrates tumor suppressor activity in multiple cancers. In lung cancer, reduced or complete loss of TGFBR3 expression correlates with increased invasion, metastasis, and angiogenesis 3. In bladder cancer, TGFBR3 suppression by the oncogenic transcription factor KLF16 promotes cell proliferation and migration 4. Conversely, elevated TGFBR3 levels show protective cardiovascular effects: genetically predicted higher TGFBR3 was inversely associated with systolic blood pressure, incident hypertension, and cardiovascular disease events across multiple cohorts 5. TGFBR3 also influences bone mineral density, with genome-wide association studies identifying TGFBR3 as a BMD candidate gene across multiple ethnic populations 6. These findings establish TGFBR3 as a multifunctional regulator with disease-suppressive roles in cancer and cardiovascular pathology.