AADACL1 metabolizes HAG to modulate PKC signaling in human platelets. Collagen binding to glycoprotein VI and α2β1 receptors initiates complex signaling cascades leading to the release of intracellular Ca²⁺ and formation of DAG, which activate the small GTPase Rap1 and PKC isoforms. PKC mediates ADP release from dense granules, which directly stimulates ADP receptors that contribute to αIIbβ3 integrin activation, fibrinogen binding, and subsequent platelet aggregation. We and others have determined that AADACL1 hydrolyzes the endogenous inhibitory lipid HAG to its inactive metabolite HG and that HAG can be rapidly converted to a phosphorylated metabolite called HAGP by an unknown lipid kinase that may be DGK. We show here for the first time that HAGP directly interacts with PKCα C1 domains and reduces kinase activity. Because HAGP is not a substrate for AADACL1, however, its levels are likely controlled by AADACL1-dependent hydrolysis of the HAGP precursor, HAG. We therefore propose that either inhibition of AADACL1 by JW480 or administration of high extracellular HAG concentrations results in accumulation of HAGP, which potentially competes for DAG binding to PKC isoforms to inhibit PKC activity and ultimately impairs ADP release and platelet aggregation.