Several authors have reported the existence of supramultiplicative behavior in signaling cascades (i.e. the ultrasensitivity of the combination of layers is higher than the product of individual ultrasensitivities), but in many cases the ultimate origin of supramultiplicativity remained elusive. Altszyler et al. (2017) framework naturally suggested a general scenario where supramultiplicative behavior could take place. This could occur when, for a given module, the corresponding Hill's input working range was located in an input region with local ultrasensitivities higher than the global ultrasensitivity of the respective dose-response curve.