ALK6

ALK6, also called BMPRIB/BMPR1B, is a BMP type I serine/threonine kinase receptor involved in skeletal development, homeostasis, and regeneration^[1]. Mechanistically, BMP ligands signal through type I and type II receptor complexes, where activated type I receptors phosphorylate SMAD effectors to initiate intracellular BMP signaling^[2]. In musculoskeletal biology, ALK6 belongs to the BMPRI group with ALK2 and ALK3, and these receptors regulate myogenesis, chondrogenesis, and osteogenesis^[1]. Compared with related isoforms, ALK6 shares high homology with ALK3 but shows distinct signaling roles under TGF-β type III receptor control^[3]. TβRIII more potently enhances ALK6-mediated BMP-responsive promoter activation and Smad6 up-regulation, while it specifically enhances ALK3-mediated ID-1 up-regulation^[3]. In disease models, childhood idiopathic pulmonary arterial hypertension patients carried BMPR1B missense mutations, and mutant BMPR1B increased SMAD8-related transcriptional activation in reporter assays^[4]. In trauma-induced heterotopic ossification, BMP signaling was required, but no single type I BMP receptor, including BMPR1b/ALK6, was individually necessary, supporting functional redundancy^[5]. For experimental applications, BMPR type I kinase inhibitors block BMP/SMAD reporter activity and BMP-induced SMAD1/5 phosphorylation in zebrafish and mammalian cells^[6].