FBXO25 is an F-box protein that functions as a substrate-recognition component of SCF-type E3 ubiquitin ligase complexes, mediating the ubiquitin-dependent degradation of multiple protein substrates. In cardiac development, FBXO25 directly interacts with and promotes degradation of key cardiac transcription factors including Tbx5, Nkx2-5, Isl1, and Mef2C, thereby regulating cardiomyocyte differentiation 12. FBXO25 also functions as a negative regulator of MAPK/ERK signaling by reducing ERK1/2 phosphorylation independently of MEK1/2, suppressing cell proliferation under growth factor stimulation 3. In cancer contexts, FBXO25 promotes disease progression: it enhances cutaneous squamous cell carcinoma growth through cyclin D1 stabilization via Oct-1 degradation 4, and drives ovarian cancer progression by upregulating α-actinin 1 (ACTN1), activating ERK1/2 signaling and promoting macrophage M2 polarization 5. In cardiac disease, FBXO25 expression decreases during myocardial infarction 1. Clinically, 8p23.2-pter microdeletions involving FBXO25 are associated with neurodevelopmental disorders, though recent evidence suggests other genes in the region may be primary contributors 6. FBXO25 dysregulation in cardiac and cancer pathologies suggests therapeutic potential in these disease contexts.