The membrane-associated RING-CH (MARCH) family of E3 ubiquitin ligases is thought to perform predominantly immunoregulatory functions by controlling the localization and abundance of a diverse array of immune receptors. However, the physiological substrates of the MARCHs remain elusive. In this issue of Immunology and Cell Biology, the group of Evelina Gatti describes a novel function for MARCH9.1 The location where this enzyme carries out ubiquitination, its substrates and the functional implications of its activity are unexpected, but provide potential explanations for the ability of MHC class I molecules (MHC I) to perform cross-presentation.