CTH and vascular dementia: Interestingly, an I428S mutation in CCM2 has been reported in a patient diagnosed with vascular dementia (CCM2I428S [Mönkäre et al., 2021]), and this isoleucine is on the same face of the CTH helix as the mutations we designed, so we predicted it too would impact the TLNRD1–CCM2 binding interface.