Adipocyte-Specific TMEM41B Deficiency Enhances Bone Formation and Attenuates Osteoporosis via the YY1-Calreticulin Axis

Osteoporosis (OP) is a prevalent skeletal disorder characterized by excessive bone marrow adiposity and impaired osteogenesis. Here, we identify TMEM41B, an endoplasmic reticulum-resident protein, as a critical regulator of bone homeostasis through its actions in bone marrow adipocytes (BMAs). Adipocyte-specific deletion of TMEM41B in mice (TMEM41B AKO) significantly increased bone mass, improved trabecular and cortical bone parameters, and enhanced mechanical strength, particularly in long bones.