Combining CRISPR-Cas9-mediated loss-of-function of RNF213 in brain endothelial cells and 3D cellular cultures, we were able to generate a reliable MMD in vitro RNF213-deficient model demonstrating reminiscent and characteristic pathological disease manifestations such as enhanced and aberrant angiogenesis. Here, RNF213 is linked to multiminicore myopathy.