In summary, we found that loss of S1PL activity in S1PL−/− mice results in severe T-cell depletion in the blood, thymus, spleen, and lymph nodes, as well as lesions in the lung, heart, urinary system, and bone, and that the observed reduced viability of S1PL−/− mice is most likely due to respiratory failure. This evidence concerns the gene SGPL1 and respiratory failure.