SP7 (Sp7 transcription factor) is a critical transcriptional activator essential for osteoblast differentiation and bone formation 1. SP7 functions downstream of RUNX2, which induces SP7 expression to convert RUNX2+ osteoprogenitors into RUNX2+SP7+ preosteoblasts 12. SP7 then drives the differentiation of preosteoblasts into mature osteoblasts without enhancing their proliferation 1. The transcription factor binds to G/C-rich DNA sequences and regulates major bone matrix protein genes including Col1a1 1. Beyond its canonical role in osteoblast differentiation, SP7 has been identified to control osteocyte dendrite formation through its target gene osteocrin 3. SP7 is necessary for osteocytes to acquire sufficient cellular processes, and reduction of these processes results in osteocyte apoptosis and cortical porosity 2. Mutations in SP7 cause osteogenesis imperfecta in rare cases, with defective osteocyte morphology observed in humans carrying SP7R316C mutation 31. Recent genome-scale analyses have revealed both canonical and non-canonical modes of SP7 action, identifying additional target genes and upstream regulatory factors that control skeletal development and maintenance 4.