Significance It is well established that the cross-talk between the plasma membrane (PM) and the endoplasmic reticulum (ER) plays an important role in neuronal signaling. Until recently, this cross-talk was thought to be mediated primarily by soluble second messengers, such as Ca ²⁺ and IP3, although it has long been known that tight appositions between the ER and the PM occur in all cells and are abundant in neurons. Investigations of the proteins that populate these contacts are shedding new light on feedback regulatory mechanisms between the two membranes. The present study identifies the phospholipid transporter TMEM24/C2CD2L as a regulated component of ER–PM contacts in neurons and suggests that lipid transfer between the two bilayers participates in the control of neuronal signaling.