Mutation of the PLEKHM1 gene has been identified as a cause of osteopetrosis in ia/ia (incisors absent) rats, as well as a subset of patients with intermediate osteopetrosis, due to diminished bone resorption and an intrinsic defect in ruffled border formation associated with the accumulation of intracellular lysosomes in osteoclasts23,32. The gene discussed is PLEKHM1; the disease is osteopetrosis.