Analyzing the proteomic landscape of iCCA-ECF obtained by iCCA patients, we unveiled the presence of an angio-inhibitory milieu, characterized by overexpression of thrombospondin 1 and 2 (THBS1, THBS2) and pigment epithelium-derived factor (PEDF) that hinder the vascular network and promote the trans-differentiation of vascular endothelial cells toward a lymphatic phenotype. Here, SERPINF1 is linked to infantile convulsions and choreoathetosis.