TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of SMAD1/5/8 specifically.308 In humans, TMEM53 was identified as a susceptibility gene for osteoporosis in several studies,309,310 and was recently associated with a previously unknown type of sclerosing bone disease (Table 2).308. Here, TMEM53 is linked to osteoporosis.