Deletion of the genes coding for either RANK or RANKL (Tnfrsf11a and Tnfsf11, respectively), blocks OCL production and leads to severe osteopetrosis in mice (Table 1) and in humans (Dougall et al., 1999; Kong et al., 1999; Kim et al., 2000; Li et al., 2000; Sobacchi et al., 2013; Palagano et al., 2018), indicating that RANK-RANKL signaling is critical for osteoclastogenesis. The gene discussed is TNFSF11; the disease is osteopetrosis.