Using primary cells isolated from Marchf1-/- and Marchf8-/- mice, we have undertaken extensive analysis of MARCH1 and MARCH8 E3 Ub ligases in an array of primary haemopoietic and non-haemopoietic cell types including traditional and non-traditional antigen presenting cells (APCs). Using flow cytometry and proteomic analysis of plasma membrane (PM) and intracellular compartments (IC), we describe unique roles for MARCH1 and MARCH 8 in haemopoietic cells and non-haemopoietic cells respectively to redefine a panel of substrates for these E3 Ub ligases in primary immune cells.