AIM Cardiac hypertrophy is regarded as a clinical determinant of heart failure.The average age of cardiac hypertrophy onset is about 50 years old and the average patient with heart failure is 77 years old.This leaves a relatively large time window where a patient displaying early cardiac hypertrophy could be treated to slow or even prevent the progression of hypertrophic remodelling; therefore studies to discover regulatory mechanisms underlying hypertrophic remodelling and to identify potential therapeutic targets for treating heart failure are of paramount importance.METHODS Over the past few years using genetically modified mouse models and pharmacological agents our group has investigated the roles of a number of intracellular signalling proteins in cardiac hypertrophy, and recently identified a novel anti-hypertrophic molecule, p21-activated kinase-1 (Pak-1).RESULTS In the heart our studies demonstrate Pakl protection against stress-induced hypertrophic remodelling and targeting of Pak-1 in heart muscle by FTY-720 via Gi coupled sphingosine receptors is able to prevent the induction of stress-induced hypertrophy and reserve existing hypertrophy and fibrosis in wild-type mice, without compromising the cardiac functions.1FTY-720 is known as a sphingosine-like analogue, derived from myriocin, a component of the natural product Isaria sinclairi.CONCLUSION Our data provides a scientific basis of development of FTY-720 for clinical applications in the treatment of cardiac hypertrophic remodelling.