Mutation or disturbance in the level of ATF4 has been associated with two human genetic skeletal system diseases, Coffin–Lowry syndrome and neurofibromatosis type I. ATF4 overexpression in fibroblasts could induce osteoblast-specific gene expression, osteocalcin synthesis, and aberrant mineral deposition.146 At the same time, ATF4 protects cells from amino acid starvation by enhancing the intakes of amino acids into cells. Here, ATF4 is linked to skeletal system disorder.