Disruption of the vascular ECM has been hypothesised to be a key component in pathogenesis of cerebral small vessel disease, particularly in monogenic forms, and several of the genes implicated in this study (COL4A2, LOX, SH3PXD2A, GPR126, HTRA1) have key roles in the ECM.70 The gene discussed is LOX; the disease is cerebral small vessel disease.