EMD and Marinesco-Sjogren syndrome: Interestingly, SIL1-deficient mice and human Marinesco Sjögren syndrome (MSS) patients lacking SIL1 also display myonuclear envelope defects.47 Consistent with this P56S-VAPB affects the retrograde trafficking of ERGIC-5349 and shuttling of emerin from the ER to the inner nuclear membrane,49 and knockdown of endogenous VAPB actually recapitulates this phenotype.49 Thus, nuclear envelope defects emerge as a common denominator of pathologies associated with the ALS proteins SigR1, VAPB and SIL1.