SMPD3 and Severe short stature: Neutral sphingomyelinase 2 (nSmase2) is encoded by the Smpd3 gene in mice and is capable of catalyzing the hydrolysis of another MV membrane phospholipid, sphingomyelin, to produce PCho with a ceramide byproduct.94 The fro mutation in the Smpd3 gene generates a distinctive phenotype with extensive musculoskeletal defects resulting in dwarfism.95, 96 Khavandgar and colleagues97 demonstrated that the fro/fro mouse exhibits delayed mineralization of the long bones and calvaria, along with impaired hypertrophy in growth plate chondrocytes during embryonic development.