This graphical abstract illustrates how RBM25 exacerbates post‐infarction heart failure in rats by promoting exon 16 skipping in MAP4K4, generating a truncated isoform (MAP4K4‐Δ16) that enhances MAP3K1 binding and activates the p38 MAPK pathway, leading to increased cardiomyocyte apoptosis via upregulated Caspase‐3 and Bax and downregulated Bcl‐2. Here, RBM25 is linked to heart failure.