Membrane metallo-endopeptidase (MME) is a membrane-bound protein with an extracellular protease domain. Ramirez et al. show that MME has distinct roles in white preadipocytes. MME can target a broad class of inflammatory cytokines, thus its high expression in subcutaneous preadipocytes may serve to decrease inflammatory responses. MME can also regulate receptor trafficking, suggesting a cellular role in insulin signaling.