RAC1 and osteopetrosis: Studies have showed that double KO of Rac1 and Rac2 in mice caused severe metaphyseal osteopetrosis due to cytoskeleton disarrangement and osteoclast dysfunction.73,74 Although Rac1/2-deficient osteoclasts in vitro and Rac1/2 KO mice exhibited bone resorption defects, the magnitude of phenotypic changes caused by lack of Rac1/2 is less severe than that of Lrrk1-deficient cells or Lrrk1 KO mice.