Proper regulation of Indian hedgehog (Ihh) signaling is vital for chondrocyte 
proliferation and differentiation in the growth plate. Its dysregulation causes 
skeletal dysplasia, osteoarthritis or cartilaginous neoplasia. Here, we show 
that Suppressor of fused (Sufu) and Kif7 are essential regulators of Ihh 
signaling. While Sufu acts as a negative regulator of Gli transcription factors, 
Kif7 functions both positively and negatively in chondrocytes. Kif7 plays a role 
in the turnover of Sufu and the exclusion of Sufu-Gli complexes from the primary 
cilium. Importantly, halving the dose of Sufu restores normal hedgehog pathway 
activity and chondrocyte development in Kif7-null mice, demonstrating that the 
positive role of Kif7 is to restrict the inhibitory activity of Sufu. 
Furthermore, Kif7 also inhibits Gli transcriptional activity in the chondrocytes 
when Sufu function is absent. Therefore, Kif7 regulates the activity of Gli 
transcription factors through both Sufu-dependent and -independent mechanisms.