Oxidative stress-responsive 1 protein (OXSR1), a protein of 527 amino acids, belongs to the STE20 subfamily. OXSR1 is one of two human homologs of Fray, a serine/threonine kinase expressed in Drosophila. OXSR1 binds to and phosphorylates p21-activated protein kinase PAK1 and regulates downstream kinases in response to environmental stress. Endogenous OXSR1 is activated only by osmotic stresses, notably sorbitol and to a lesser extent NaCl. OXSR1 may also play a role in regulating the actin cytoskeleton. The chloride channel proteins SLC12A1, SLC12A2, and SLC12A6 isoform 2 interact with OXSR1, but SLC12A4 and SLC12A7 do not. The WNK1 and WNK4 protein kinases activate OXSR1 by phosphorlating its T-loop. The OXSR1 protein is widely expressed in mammalian tissues.