FKBP12 as a regulator of BMP/SMAD signaling. (A) When bound to ALK2, FKBP12 limits phosphorylation of SMAD 1/5/8 in response to canonical BMP signaling ligands. Upon release of FKBP12, which can occur either by mutation of ALK2 or by drug-mediated sequestration of FKBP12, ALK2 demonstrates enhanced signaling that is independent of ligand binding and phosphorylation by BMP type II receptors (B) and hyperresponsiveness to canonical BMP ligands and acquired responsiveness to the inflammatory ligand, activin A (C).