ASB2 (ankyrin repeat and SOCS box containing 2) is an E3 ubiquitin ligase that regulates protein degradation through the proteasome-mediated pathway. Its primary function is targeting filamin A (FLNA) and filamin B (FLNB) for proteasomal degradation 1, with secondary substrates including SMAD9 2. ASB2-mediated filamin degradation promotes actin cytoskeleton remodeling essential for multiple cellular processes: hematopoietic cell adhesion to fibronectin, dendritic cell migration through podosome formation, and NK cell migration 3. In cardiogenesis, ASB2 is critical for embryonic survival and proper heart development; Asb2 deletion causes congenital double outlet right ventricle (DORV) through FLNA accumulation and dysregulated TGFβ/Smad signaling 4. ASB2 also regulates BMP signaling by degrading SMAD9, with developmental importance demonstrated in zebrafish cardiac models 2. Disease relevance includes acute myeloid leukemia, where ASB2 expression is repressed by BCL11A, promoting malignant progression 5, and where FTO-mediated m6A demethylation affects ASB2 mRNA levels 6. ASB2 represents a therapeutic target in cancer and developmental heart disease, with potential clinical applications in immunotherapy and leukemia treatment.