TMEM263 encodes a plasma membrane protein essential for postnatal skeletal growth and development 1. The protein plays a critical role in regulating the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis, which controls longitudinal bone growth 1. Mechanistically, TMEM263 is required for maintaining hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling; loss of TMEM263 results in reduced circulating IGF-1 levels and impaired growth plate development 1. Clinically, TMEM263 mutations cause severe skeletal dysplasia in humans. A homozygous frameshift mutation was identified in a fetus with severe lethal skeletal dysplasia characterized by rhizomelic dysplasia and pathologic rib shortening, representing the first documented human case 2. Mouse knockout studies confirm TMEM263's causal role, demonstrating that Tmem263-null mice develop proportional dwarfism and impaired skeletal acquisition with dramatic growth deficits appearing by postnatal day 21 1. SNP variants in TMEM263 are associated with bone mineral density in humans 1, and the gene was previously implicated in dwarfism in chickens via a nonsense mutation 3. These findings establish TMEM263 as a novel candidate gene for growth disorders and suggest that TMEM263 mutations may cause GH insensitivity and impair linear growth in humans 1.