Given previous findings and that mutations of Trp53 and Rb1 often occur in osteosarcoma patients, in this study we examined whether deletions of Trp53 and Rb1 in Ctsk-expressing cells can cause osteosarcoma formation and progression and affect Hippo pathway by generating and analyzing Ctsk-Cre;Trp53f/f/Rb1f/f mice. The gene discussed is CTSK; the disease is osteosarcoma.