IFITM5 is an osteoblast-specific transmembrane protein essential for normal bone mineralization and skeletal development 1. Primary function: IFITM5 acts as a positive regulatory factor for mineralization in vitro and is required for proper bone formation 1. Mechanistically, IFITM5 marks cranio-maxillofacial skeletal stem cells (CMSSCs) located in the periosteum, where these IFITM5+ cells exhibit strong osteogenic differentiation capacity and self-renewal, orchestrating intramembranous ossification of craniofacial bones 2. Disease relevance: IFITM5 mutations cause osteogenesis imperfecta (OI), a heterogeneous skeletal dysplasia characterized by bone fragility and deformity 3. The recurrent dominant mutation c.-14C>T in IFITM5's 5' untranslated region causes OI type V, distinguished by hyperplastic callus formation and interosseous membrane calcification 4. This mutation impairs osteo-chondroprogenitor differentiation through aberrant ERK/SOX9 signaling, reducing osteoblast formation from chondrogenic precursors 5. Clinical significance: IFITM5 mutations account for 9% of moderate-to-severe OI cases 6. IFITM5 overexpression promotes osteogenic differentiation and tumor cell apoptosis, suggesting therapeutic potential for targeting this pathway in bone disorders and osteosarcoma 7.