Even though S1P mutations in humans are yet to be reported, mutations in SREBP-2 (a major S1P/S2P substrate) are linked to osteoarthritis pathogenesis in humans (Kostopoulou et al., 2012), and mutations in S2P are linked to osteogenesis imperfecta (Lindert et al., 2016). This evidence concerns the gene MBTPS1 and osteoarthritis.