Although a direct interaction between IPAF and an activating ligand has not been demonstrated, IPAF can be activated by cytosolic flagellin either applied experimentally or resulting from the activity of the virulence-associated type III or V secretion systems (Franchi et al. 2006, Miao et al 2007, 2008). Activation can also be flagellin-independent (Suzuki et al. 2007, Sutterwala et al. 2007), suggesting alternative mechanisms that are likely to involve recognition of components of the bacterial type III secretion system (Miao et al. 2010). The LRR domain of IPAF appears to repress activity in the absence of a ligand as removal of this domain leads to constitutive activation (Poyet et al. 2001).