NPCs regulate many physiologically essential processes throughout the lifecycles of cells and tissue, including homeostasis, differentiation, gene expression, and proliferation.11–16 Like CME, upregulation of NPC transport is associated with diverse pathologies, including the malignant transformation of cancer cells (Fig. 1), to meet their substantial proliferation rate.17,18 Both clathrin coats and NPC scaffold proteins are rich in β-propeller folds.6,7,19 Such folds are particularly abundant in NPC scaffold proteins (Fig. 1). The gene discussed is NPC1; the disease is cancer.