Human UFSP2 Y290, D426, and H428 are equivalent to mouse Ufsp2 Y282, D418, and H420 (Fig. 4c), which contribute to the catalytic core in the active site of the mouse protein.27 Mutating Y282 to His inactivated Ufsp2’s catalytic activity.27 These data suggest that variants observed in human skeletal dysplasias impact UFSP2’s catalytic activity, but the V115E variant in patients with neurological disorders may have other effects including reduced protein stability and possibly reduced interaction with UFMylated targets. This evidence concerns the gene UFSP2 and skeletal dysplasia.