SMAD2 and osteoporosis: Sotatercept, initially developed totreat osteoporosis, is a fusion protein consisting of the extracellular domain ofhuman activin receptor type IIA and the Fc domain of IgG1 which serves as aligand trap for members of the TGF-β superfamily thereby decreasingpro-growth SMAD2/3 signaling to restore balance with the growth-inhibitingSMAD1/5/9 signaling diminished by BMPR2 insufficiency [48].