Rare vascular diseases such as hereditary haemorrhagic telangiectasia (HHT) represent a big challenge in biomedicine: complex pathomechanisms, limited patient material, and fragmented research communities slow down therapeutic progress. We argue that two elements are pivotal to bypass this problem. First, genuine partnership with patients—ranging from biospecimen donation to agenda setting—can unlock critical resources and align research with real-world needs. Second, molecular intersections between HHT and related pathologies call for coordinated, cross-disease programmes rather than isolated efforts. Recent multi-stakeholder gatherings hosted by patient organisations in Germany and elsewhere, such as the Second Scientific Symposium by the German HHT self-help group (Morbus Osler Selbsthilfe e.V.) in May 2025, have shown that when clinicians, basic scientists from different disciplines, and affected families co-design research questions, novel in vitro models can be generated more accurately, and pragmatic clinical trials emerge. Here, we outline actual opportunities for patient-integrated cellular model systems, shared biobanking, and comparative approaches across vascular malformation syndromes. In our opinion, letting informed and well-organised patient communities assemble such meetings opens unique opportunities twofold: on the one hand, the field can finally break out of its disease-specific silos; on the other hand, the development of novel HHT therapies could be accelerated by learning from progress in related pathologies.

Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs). Targeting of Bmpr2 reduced sprouting angiogenesis in zebrafish and BMPR2-deficient human ECs formed fewer filopodia, affecting cell migration and actomyosin localization. Spheroid assays revealed a reduced sprouting of BMPR2-deficient ECs in fibrin gels. Even more strikingly, in mosaic spheroids, BMPR2-deficient ECs failed to acquire tip-cell positions. Yet, 3D traction force microscopy revealed that these distinct cell behaviors of BMPR2-deficient tip cells cannot be explained by differences in force-induced matrix deformations, even though these cells adopted distinct cone-shaped morphologies. Notably, BMPR2 positively regulates local CDC42 activity at the plasma membrane to promote filopodia formation. Our findings reveal that BMPR2 functions as a nexus integrating biochemical and biomechanical processes crucial for TCs during angiogenesis.