Four-and-a-half LIM domains protein 2 (FHL2) is a modular adaptor protein composed entirely of LIM domains that mediate protein–protein interactions linking the cytoskeleton to transcriptional regulation. In this study, full-length human FHL2 was recombinantly expressed in Escherichia coli and purified without affinity tags. The protein was biophysically and structurally characterized using size-exclusion chromatography coupled to static light scattering (SEC-SLS), small-angle X-ray scattering (SEC-SAXS), and chemical cross-linking coupled to mass spectrometry (XL-MS). Integrative structural analysis based on SAXS and XL-MS data was used to investigate the conformational landscape of FHL2 in solution, revealing the presence of both extended and compactly bent conformations.