J Cell Mol Med. 2026 May;30(9):e71160. doi: 10.1111/jcmm.71160.
ABSTRACT
Sorbin and SH3 Domain Containing 2 (SORBS2), a multifunctional scaffold protein harbouring Sorbin homology (SoHo) and Src homology 3 (SH3) domains, serves as a molecular hub in human diseases by integrating cytoskeletal remodelling, signal transduction and RNA metabolic regulation. This study systematically analyses SORBS2's molecular features, expression regulatory mechanism and disease associations. In oncology, it suppresses metastasis via enhancing the stability of certain mRNAs and immunomodulation yet exhibits oncogenic properties in triple-negative breast cancer. Cardiovascular manifestations demonstrate dose-sensitive pathology: deficiency causes arrhythmogenic cytoskeletal disorganization, while overexpression induces β-tubulin hyper polymerization and ventricular maldevelopment. Epigenetic silencing by miR-484 exacerbates metabolic liver disease, whereas defective interaction with the large-conductance Ca2+-activated K+ (BK) channel drives diabetic vasculopathy. Neurologically, it modulates synaptic remodelling and neuroinflammatory pathways. Functioning as a signalling nexus, SORBS2 interconnects chronic inflammation, oxidative stress and metabolic dysfunction, supporting 'one target for multiple diseases' strategy. Future research requires integration of single-cell omics, Artificial intelligence (AI)-based drug design and epigenetic editing for clinical translation.
PMID:42045927 | DOI:10.1111/jcmm.71160