FRS3 (fibroblast growth factor receptor substrate 3) is an adapter protein that functions as a critical mediator in neurotrophin and growth factor signaling pathways. FRS3 binds to all neurotrophin Trk receptor tyrosine kinases and becomes tyrosine phosphorylated in response to NGF, BDNF, NT-3, and FGF stimulation 1. The protein contains conserved binding sites for signaling molecules Grb2 and Shp2, enabling downstream activation of MAP kinase signaling cascades 1. Unlike the related adapter FRS2, FRS3 exhibits unique subcellular localization and functions as a microtubule-associated protein, binding microtubules comparably to MAP2 2. During development, FRS3 shows a more restricted expression pattern than FRS2, being predominantly expressed in the ventricular layer of the developing neural tube and brain 32. FRS3 is also activated by thyroid TRK oncoproteins, suggesting potential involvement in thyroid carcinogenesis 4. Recent genome-wide association studies have identified FRS3 missense variants that significantly affect body mass index across diverse populations, establishing FRS3 as a BMI-associated gene that acts downstream of the BDNF-TrkB pathway to regulate appetite, food intake, and energy expenditure 5. Additionally, FRS3 has been implicated in synthetic lethal interactions with TP53 in blood cancers 6.