Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C. elegans reveals that the intracellular active zone protein SYD-1 accumulates at nascent presynapses prior to its binding partner neurexin. Combining molecular dynamics simulations to model intrinsic interactions between SYD-1 and lipid bilayers with biochemical and in vivo validation of these predictions, we find that PIP