From Genetic Prioritization to Therapeutic Validation: Interpreting C4B in Calcific Aortic Valve Stenosis.

Li et al. identified C4B as a potential therapy target for calcific aortic valve stenosis using genetic and histological analyses. However, genetic target prioritization isn't the same as pharmacological validation. Lifelong genetic differences in C4B may not replicate therapeutic inhibition effects, especially given the complex C4A/C4B locus. Increased C4B in calcified valves supports biological relevance but doesn't prove causality. C4B is a promising candidate needing further functional and pharmacological validation.