ARHGAP28 is a Rho GTPase activating protein that functions as a negative regulator of RhoA signaling by converting active GTP-bound RhoA to its inactive GDP-bound state 1. The protein plays a crucial role in cytoskeletal regulation, as overexpression of ARHGAP28 reduces basal RhoA activation and disrupts actin stress fibers in osteosarcoma cells 1. During development, ARHGAP28 shows temporal expression patterns, with expression detected in soft tissues at E12.5, pre-bone structures at E15.5, and prominent expression in ribs and limb bones at E18.5 1. The gene demonstrates upregulation during Rho-dependent extracellular matrix assembly, suggesting involvement in mechanically strong tissue development 1. In disease contexts, ARHGAP28 expression serves as a potential biomarker, being notably overexpressed in podocytes in diabetic nephropathy models and human kidney tissues 2. The protein also shows tumor suppressor properties, as ARHGAP28 overexpression inhibits proliferation, migration, and invasion in osteosarcoma cells both in vitro and in vivo 3. Additionally, ARHGAP28 has been implicated in cancer stem cell gene networks in meningiomas 4 and identified as a candidate susceptibility gene in migraine without aura 5.