To test this hypothesis, the objectives of this study were to (1) characterize the dynamic expression pattern of NPC1L1 during osteogenic differentiation and its association with osteoporosis (RO1); (2) determine whether NPC1L1 regulates osteogenic activity through cholesterol metabolism independently of its transport function (RO2); and (3) elucidate the molecular mechanism of the NPC1L1/C/EBPα/Cyp27a1/27‐OHC axis (RO3). This evidence concerns the gene NPC1L1 and osteoporosis.