Smooth muscle contraction in the cardiovascular system, airways, prostate and lower urinary tract is involved in the pathophysiology of many diseases, including cardiovascular and obstructive lung disease plus lower urinary tract symptoms, which are associated with high prevalence of morbidity and mortality. This prominent clinical role of smooth muscle tone has led to the molecular mechanisms involved being subjected to extensive research. In general smooth muscle contraction is promoted by three major signalling pathways, including the monomeric GTPase RhoA pathway. However, emerging evidence suggests that monomeric GTPases other than RhoA may be involved in signal transduction in smooth muscle contraction, including Rac GTPases, cell division control protein 42 homologue, adenosine ribosylation factor 6, Ras, Rap1b and Rab GTPases. Here, we review these emerging functions of non‐RhoA GTPases in smooth muscle contraction, which has now become increasingly more evident and constitutes an emerging and innovative research area of high clinical relevance.
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