Appearance of PI-4,5-P₂ on the granule membrane upon hemifusion may delay or inhibit full fusion by misdirecting PI-4,5-P₂–dependent reactions. The functions of several proteins in the fusion pathway (e.g., synaptotagmin, CAPS, and Munc13) require binding to PI-4,5-P₂. It is generally thought that these interactions occur with plasma membrane PI-4,5-P₂. The functions of these proteins may be thwarted if the proteins interact with PI-4,5-P₂ on the granule membrane before full fusion. The cartoon illustrates how the membrane interaction of a granule protein such as synaptotagmin would be altered by the appearance of PI-4,5-P₂ in the granule membrane.