IFI16 and familial dilated cardiomyopathy: Our study provides compelling multi-level evidence, spanning human iPSC-derived cardiomyocytes (iPSC-CMs), ex vivo human heart tissue, in vivo murine models, and single-cell transcriptomics, that establishes a critical pathogenic axis linking DDR activation to interferon-inducible protein 16 (IFI16)-mediated extracellular matrix (ECM) remodeling in DCM.