ELFN2 (Extracellular leucine-rich repeat and fibronectin type III domain-containing protein 2), also known as protein phosphatase 1 regulatory subunit 29, is a member of the extracellular Leucine-Rich Repeat superfamily (1). Expressed mainly in the nervous system, ELFN2 is a transmembrane protein that inhibits the activity of protein phosphatase 1 (PP1) complexes (2). Mature human ELFN2 consists of a 375 aa extracellular domain (ECD), a 21 aa transmembrane segment and a 402 aa cytoplasmic tail. The ECD includes one fibronectin type-III domain, five leucine-rich repeats (LRR) and one LRR C-terminal (LRRCT) domain. Human ELFN2 shares 98% aa sequence identity with mouse and rat ELFN2. Expression of ELFN2 is quite restricted to the nervous system in which it is broadly expressed in the cortex in presumed glutamatergic neurons, in hippocampal pyramidal and granule cells, and in the striatum. These patterns are maintained in adults. Given the functions and discrete patterns of many known LRR family proteins it has been proposed that ELFN2 could provide the requisite specificity of cellular interactions to mediate a large number of selective connectivity decisions involved in neurite outgrowth, axon guidance, fasciculation, and synapse formation (1). Mutations of ELFN2 have been reported in pancreatic cancer radiation resistance (3) and stress fracture (4).