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Staphylococcus aureus is a Gram-positive opportunistic pathogen capable of causing lifethreatening infections. A series of regulators controls expression of an array of virulencefactors which allow for S. aureus to infect a host. During investigation into small proteinencoding small RNAs, we identified a novel small protein regulator named ScrA.Overexpression of ScrA led to increased clumping, hemolysis, and biofilm formation,which was shown to be dependent upon the SaeRS two-component system, whilemutation of scrA lead to alterations in host factor binding, increased membrane stability,and an overall decrease in virulence. Further investigation into the mechanism of ScrAactivity revealed several amino acids essential to function residing within thetransmembrane domain. Additionally, we identify the transmembrane domain as the keydomain for ScrA function. Interaction partners were identified by both in vivo Co-Immunoprecipitations A pulldown of the ScrA promoter region identified the regulatoryprotein TcaR giving a potential link to the AlrR system. Taken together, these data revealthat ScrA acts as a novel regulator of virulence in S. aureus and may act as a nichespecific link between the Arl and Sae systems.