Beige adipocytes are thermogenic adipocytes with developmental and anatomical properties distinct from those of classical brown adipocytes. Recent studies have revealed several key molecular regulators of beige adipocyte development. CD105, also called endoglin, is a membrane protein composed of TGF-β receptor complex. It regulates TGF-β-family signal transduction and vascular formation in vivo. We report here that CD105 maintains the thermogenic gene program of beige adipocytes by regulating Smad2 signaling. Cd105-/- adipocyte precursors showed augmented Smad2 activation and decreased expression of thermogenic genes such as Ucp1 and Prdm16-which encodes a transcriptional regulatory protein for thermogenesis-after adipogenic differentiation. Smad2 signaling augmentation by the constitutively active form of Smad2 decreased the expression of thermogenic genes in beige adipocytes. Loss of thermogenic activity in Cd105-/- beige adipocytes was rescued by Prdm16 expression. These data reveal a novel function of CD105 in beige adipocytes: maintaining their thermogenic program by regulating Smad2 signaling.