RIM proteins are scaffolding molecules at the active zone of central and peripheral nervous system synapses. As a result of their interactions with multiple presynaptic active-zone proteins, synaptic vesicle proteins, and cytosolic proteins, RIMs are necessary for the efficient regulation of neurotransmitter release, short-term synaptic plasticity, and long-term synaptic plasticity. Absence of RIM1. α in knockout mice results in abnormal learning and memory and locomotor response to novelty while sparing other behaviors. This article reviews the molecular, synaptic, and behavioral findings implicating RIM proteins as key presynaptic active-zone molecules that are critical for normal central nervous system function.. . © 2009 Elsevier Ltd All rights reserved.