The results of the present study showing the crucial role of the SGPL1/S1P/S1PR axes for essential cellular processes like energy metabolism and autophagy might also explain the extensive range of anomalies reported for SPLIS, including hydrops fetalis, immunodeficiency, acanthosis, renal and adrenal insufficiencies and neurological failures. The gene discussed is MBTPS1; the disease is Immunodeficiency.