In humans, no diseases or lipid-associated traits have been associated with mutations in SYVN1,48 even though levels of this E3 may be involved in the development of multiple sclerosis and Alzheimer's disease.49,50 Further studies on the role of SYVN1/HRD1 in VLDL assembly and secretion are therefore clearly warranted. Here, SYVN1 is linked to multiple sclerosis.